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Stem Cells

European research projects

involving stem cells in the

6th Framework Programme

Stem CellsEuropean research projects involving stem cells in the 6th Framework Programme

European Commission - Directorate General for Research

Life Sciences, Genomics and Biotechnologies for Health

EUROPEAN COMMISSION

Edited by:Gwennaël Joliff-BotrelPascale Perrin

Table of contentcover 0

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INTRODUCTION - Stem cells and European Union funded research 2 7

Introduction and glossary 9

UNDERSTANDING - Fundamental knowledge relevant to human health 9

CELLS INTO ORGANS Functional genomics for development and disease of mesodermal organ systems 1 11DNA REPAIR DNA damage response and repair mechanisms 1 12EMBRYOMICS Embryomics: reconstructing in space and time the cell lineage tree 1 13EPISTEM Role of p63 and related pathways in epithelial stem cell proliferation and differentiation and in

rare EEC-related syndromes1 14

ESTOOLS Platforms for biomedical discovery with human ES cells 1 15EUCOMM The European Mouse Genome Mutagenesis Program 1 16EUGENE2 European network on functional genomics of type 2 diabetes 1 17EuReGene European renal genome project 1 18EURO-Laminopathies Nuclear envelope-linked rare human diseases: From molecular pathophysiology towards

clinical applications1 19

EuroBoNet European network to promote research into uncommon cancers in adults and children: Pathology, biology and genetics of bone tumors

1 20

EuroHear Advances in hearing science: from functional genomics to therapies 1 21EUROPEAN MCL NETWORK European Mantle Cell Lymphoma Network: Translational determination of molecular

prognostic factors and pharmacogenomics in a European interdisciplinary collaboration1 22

EURYTHRON Molecular Control of Erythropoiesis 1 23EuTRACC European Transcriptome, Regulome and Cellular Commitment Consortium 1 24EVI-GENORET Functional genomics of the retina in health and disease 1 25FunGenES Functional genomics in engineered ES cells 1 26HeartRepair Heart failure and repair 1 27INTERDEVO Gene networks in cortical interneuron development: modeling interneuron function in health

and disease1 28

LYMPHANGIOGENOMICS Genome-wide discovery and functional analysis of novel genes in lymphangiogenesis 1 29MCSCs Migrating cancer stem cells in breast and colon cancer 1 30MSCNET Myeloma stem cell Network. A translational programme identifying and targeting the early

myeloma cell hierarchy1 31

MUGEN Integrated functional genomics in mutant mouse models as tools to investigate the complexity of human immunological disease

1 32

MYORES Multi-organismic approach to study normal and aberrant muscle development, function and repair

1 33

ONCASYM Cancer stem cells and asymmetric division 1 34Plurigenes Pluripotency associated genes to de-differentiate neural cells into pluripotent cells 1 35REGULATORY GENOMICS Advanced genomics instruments, technology and methods for determination of transcription

factor binding specificities; applications for identification of genes predisposing to colorectal cancer

1 36

SIROCCO Silencing RNAs: organisers and coordinators of complexity in eukaryotic organisms 1 37THE EPIGENOME Epigenetic plasticity of the genome 1 38TRANSCODE Novel tool for high-throughput characterization of genomic elements regulating gene

expression in chordates2 39

DEVELOPING - Tools for new therapies and medicines 41

Anti-tumor targeting Modulation of the recruitment of vessels and immune cells by malignant tumors: Targeting of tumor vessels and triggering of anti-tumor defense mechanisms

1 43

CONSERT Concerted safety & efficiency evaluation of retroviral transgenesis in gene therapy of inherited diseases

1 44

CRYSTAL CRYo-banking of Stem cells for human Therapeutic AppLication 1 45E.E.T.-Pipeline European Embryonal Tumor Pipeline 1 46EPI-VECTOR Episomal vectors as gene delivery systems for therapeutic applications 1 47EURO-THYMAIDE Novel approaches to pathogenesis, diagnosis and treatment of autoimmune diseases based

on new insights into thymus-dependent self-tolerance1 48

EuroCSC Targeting cancer stem cells for therapy 1 49EUROSTEMCELL European consortium for stem cell research 1 50EUROXY Targeting newly discovered oxygen-sensing cascades for novel cancer treatments: Biology,

equipment, drug candidates1 51

EVGN European Vascular Genomics Network 1 52GIANT Gene therapy: an integrated approach for neoplastic treatment 1 53INTHER Development and application of transposons and site-specific integration technologies as

non-viral gene delivery methods for ex vivo gene-based therapies1 54

KIDSTEM Developing a Stem Cell Based Therapy to Replace Nephrons Lost through Reflux Nephropathy

1 55

magselectofection Combined isolation and stable nonviral transfection of hematopoietic cells ? a novel platform technology for ex vivo hematopoietic stem cell gene therapy

1 56

MODEST Modular devices for ultrahigh-throughput and small volume nucleofection 1 57MOL CANCER MED Developing molecular medicines for cancer in the post genome era based on telomerase and

related telomere-maintenance mechanisms as targets1 58

MYOAMP Amplification of human myogenic stem cells in clinical conditions 1 59NEURONE Molecular mechanisms of neuronal degeneration: from cell biology to the clinic 1 60NEUROscreen The Discovery of Future Neuro-therapeutic Molecules 1 61NSR Nervous System Repair 1 62OsteoCord Bone from blood: Optimised isolation, characterisation and osteogenic induction of

mesenchymal stem cells from umbilical cord blood1 63

SKINTHERAPY Gene therapy for Epidermolysis Bullosa: a model system for treatment of inherited skin diseases

1 64

STEM-HD Embryonic stem cells for therapy and exploration of mechanisms in Huntington Disease 1 65STEMS Pre-clinical evaluation of stem cell therapy in stroke 1 66SyntheGeneDelivery Ex vivo gene delivery for stem cells of clinical interests using synthetic processes of cellular

and nuclear import and targeted chromosomal integration1 67

TherCord Development and preclinical testing of cord blood-derived cell therapy products 1 68TUMOR-HOST GENOMICS Genome-wide analysis of signaling pathways in regulation of the interactions between tumor

and host cells: Applications for cancer therapy 1 69

X-ALD X-linked adrenoleukodystrophy (X-ALD): pathogenesis, animal models and therapy 1 70

BUILDING - Tissue engineering 2 71

3G-SCAFF Third generation scaffolds for tissue engineering & regenerative medicine 1 73AUTOBONE Production unit for the decentralised engineering of autologous cell-based osteoinductive

bone substitutes1 74

BARP+ Development of a bioartificial pancreas for type I diabetes therapy - nanotechnology biomaterial engineering transplantation

1 75

BIOSYS Intelligent biomaterial systems for cardiovascular tissue repair 1 76CellPROM Cell programming by nanoscaled devices 1 77CORNEA ENGINEERING Three-dimensional reconstruction of human corneas by tissue engineering 1 78Custom-IMD SME supply chain integration for enhanced fully customisable medical implants, using new

biomaterials and rapid manufacturing technologies, to enhance the quality of life for eu citizens

1 79

EXPERTISSUES Novel therapeutic strategies for tissue engineering of bone and cartilage using second generation biomimetic scaffolds

1 80

GENOSTEM Adult mesenchymal stem cells engineering for connective tissue disorders. From the bench to the bed side

1 81

HIPPOCRATES A hybrid approach for bone and cartilage tissue engineering using natural origin scaffolds, progenitor cell and growth factors

1 82

LIVEBIOMAT Development of new polymeric biomaterials for in vitro and in vivo liver reconstruction 1 83NANOBIOCOM Intelligent nanocomposite for bone tissue repair and regeneration 1 84NanoEar 3g-Nanotechnology based targeted drug delivery using the inner ear as a model target organ 1 85

NEWBONE Development of load-bearing fibre reinforced composite based non-metallic biomimetic bone implants

1 86

SILKBONE Development and evaluation of mineralized silk based composites for orthopaedic applications

1 87

SmartCaP Injectable macroporous biomaterial based on calcium phosphate cement for bone regeneration

1 88

STEPS A systems approach to tissue engineering processes and products - biomaterial engineering biomedical engineering nanotechnology

2 89

VASCUPLUG Bioreactive composite scaffold design for improved vascular connexion of tissue-engineered products

2 91

MODELLING - Mathematical & biology models, alternatives to animals testing 2 93

ARTEMIS In Vitro Neural Tissue System For Replacement Of Transgenic Animals With Memory / Learning Deficiencies

1 95

CARCINOGENOMICS Development of a high throughput genomics-based test for assessing genotoxic and carcinogenic properties of chemical compounds in vitro

1 96

CONTROL CANCER STEM Developing a virtual and molecular control board for diverting cancer stem cell to non-malignance

1 97

INVITROHEART Reducing Animal Experimentation in Drug Testing by Human Cardiomyocyte In Vitro Models Derived from Embryonic Stem Cells

1 98

M3CS-TU TH Modeling, Mathematical Methods and Computer Simulation of Tumour Growth and Therapy 1 99NEURO Towards the neuronal machine 1 100PREDICTOMICS Short-term in vitro assays for long-term toxicity 1 101ReProTect Development of a novel approach in hazard and risk assessment or reproductive toxicity by a

combination and application of in vitro, tissue and sensor technologies1 102

VITROCELLOMICS Reducing Animal Experimentation in Preclinical Predictive Drug Testing by Human Hepatic In Vitro Models Derived from Embryonic Stem Cells

2 103

REPAIRING - Towards clinical applications for diseases and impairements 2 1051

BETACELLTHERAPY Beta cell programming for treatment of diabetes 1 107EuroSTEC Soft tissue engineering for congenital birth defects in children: new treatment modalities for

spina bifida, urogenital and abdominal wall defects1 108

MYOCARDIAL REPAIR Clinical experience with bone marrow cells and myoblasts transplantation for myocardial repair

1 109

RESCUE From stem cell technology to functional restoration after spinal cord injury 1 110SC&CR Application and process optimization of human stem cells for myocardium repair 1 111STEMSTROKE Towards a stem cell therapy for stroke 1 112STROKEMAP Multipotent Adult Progenitor Cells to treat Stroke 1 113THERAPEUSKIN Ex vivo gene therapy for recessive dystrophic epidermolysis bullosa: pre-clinical and clinical

studies1 114

Ulcer Therapy Gene transfer in skin equivalents and stem cells: novel strategies for chronic ulcer repair and tissue regeneration

2 115

1

TREATING - Improvement of standard hematopoeitic stem cell transplantation 117

ALLOSTEM The development of Immunotherapeutic strategies to treat haematological and neoplastic diseases on the basis of optimised allogeneic stem cell transplantation

1 119

CLINT Facilitating International Prospective Clinical Trials in Stem Cell Transplantation 1 120EUROPEAN LEUKEMIA NET Strengthen and develop scientific and technological excellence in research and therapy of

leukemia (CML, AML, MDS, CLL, adult ALL) by cooperation and integration of the leading national leukemia networks and groups in Europe

3 121

FIRST Further improvement of radiotherapy of cancer through side effect reduction by application of adult stem cell therapy

1 124

RISET Reprogramming the immune System for the Establishment of Tolerance 1 125STEMDIAGNOSTICS The development of new diagnostic tests, new tools and non-invasive methods for the

prevention, early diagnosis and monitoring for haematopoietic stem cell transplantation1 126

TRANS-NET Identification of genomic and biological markers as predictive/diagnostic/therapeutic tools for use in allogeneic stem cell transplantation: Translational research towards individualised patient medicine

1 127

TRIE Transplantation Research Integration across Europe 1 128

INTEGRATING - Ethics, legal, societal aspects, training 2 129

EMRS A European multimedia repository of science - video 1: stem cells to repair the heart 1 131EU hESC registry European human embryonic stem cell registry 1 132EUROCITS Europe, its citizens and stem cell research: a one-day conference 1 133imgbchimerashybrids Chimeras and hybrids in comparative European and international research – scientific,

ethical, philosophical and legal aspects1 134

INDUSTRYVECTORTRAIN European labcourse: Advanced methods for industrial production, purification and characterisation of gene vectors

1 135

INVIVOVECTORTRAIN European labcourse: Towards clinical gene therapy: preclinical gene transfer assessment 1 136REPROGENETICS Reprogenetics: the ethics of men making men 1 137SENECA From Cellular Senescence and Cell Death to Cancer and Ageing 1 138StemCellPatents Stem cell patents: European patent law and ethics 1 139Worldwide study A worldwide study of umbilical cord cell banking 1 140

Introduction and glossary 141

ANNEX - Classification of projects by tissues, organs and diseases 2 141

INTRODUCTION

Tissues and organs in the body are made of specialised cells that assure their specific functions. Maintenance and repair of these tissues and organs depend upon resident unspecialised adult stem cells. They are still at an early stage of development and retain the potential to turn into the different types of cells of that tissue or organ.

In bones, some typical adult stem cells, the bone marrow stem cells, give rise to all kinds of blood cells. Apart from those of the blood cell lineage, other stem cells are found in the bone, which are able to mature into cells specific to bone, cartilage, fat, tendons, muscle and heart.

During pregnancy, cells from bone marrow of the developing foetus find their way into the umbilical cord and placenta. Research suggests that umbilical cord blood stem cells, less mature than those from adult bone marrow, might be induced to turn into non-blood cells. The only cells that can evolve into any cells in the body are found in few day-old fertilised eggs, and are called embryonic stem cells.

Stem cells are crucial for a healthy organism

Stem cells play a central role in the normal growth and development of animals and humans. They have three properties that distinguish them from other cell types and make them interesting to scientists: - they are unspecialised- they are able to divide and produce copies of themselves- they have the potential to produce other cell types.

Stem cells are central to many research areas

Stem cells provide an ideal model to understand the development of organisms under healthy and disease condition. It should help decrease animal use.

Stem cells are expected to offer means to develop new families of drugs and new therapies: harnessing cell specialisation will lead to regenerative medicine.

Stem cells are daily used to treat cancer: bone marrow grafts have been used against leukemias for 30 years. Research is done to extent this approach.

Stem cells are experimentally used to repair injured organs or to fix degenerative diseases. They are injected into the body, often after being modified.

Stem cells are used to build new tissues outside the body, to be grafted, or used for toxicology testing. Applications are now scarce but are expected to grow.

Research on human embryonic stem cells, a tiny part of the overall research on stem cells, raises several ethical issues. They are addressed by national legislation worldwide.

The use of some stem cells is a matter of debate

Each type of stem cell (adult, foetal and embryonic), in humans and animals, is a glance at a different moment of a global dynamic process. Only a partial knowledge can be expected from research done on one type of stem cells.

Research needs to study stem cells of all origins

What are stem cells ?

STEM CELLS

The European Union funds projects involving stem cells

Academic organisations, corporates, individual scientists, members of the civil society, can be partners of a FP6 project.

Participation of industry (IND), in particular of Small and Medium-sized Entreprises (SMEs), is highly encouraged, as it is essential that discoveries are transformed into products or services able to improve well being and health of people. In addition, a dynamic and innovative private sector is crucial for the European Union economy and employment.

THE EUROPEAN UNION AND STEM CELLS

A CATALOGUE OF EU-FUNDED PROJECTS

The European Union funds collaborative research projects, under the 6th Framework Programme (2002-2006). In several fields of research, some of the funded projects involve stem cells, either studying stem cells themselves, or using them as discovery means or biological tools in a broader context.

The 6th Framework Programme: five kind of projects for complementary objectives

Integrated Projects (IP) adress major needs of society, by delivering knowledge for new products, processes or services

Networks of excellence (NoE) use networking to overcome European research fragmentation in defined domains, strengthening and spreading scientific and technological excellence at the European level

Specific Targeted Research Projects (STREP) focuses on very specific issues, to gain knowledge or improve existing products, processes or services, or demonstrate the viability of new technologies

Coordinated actions (CA) co-ordinate research organisations, initiatives or projects for a specific purpose

Specific Support Actions (SSA) support the Framework Programme, through events, networks, studies, stimulations of innovation..., or help building future Community research policies.

The 6th Framework Programme: research and discovery at the service of the whole society

All the listed projects in this book have at least one component of stem cell research, or use stem cells as research tools. Projects which only use stem cells as non-specific tools, in particular to create animal models, are nevertheless not included, since such techniques are used by almost all life science laboratories on a daily basis.

We chosed to organise the FP6 projects related to stem cells in a way reflecting the discovery process: understanding the biological issues, building tools (conceptual and technological), using knowledge and tools for clinical applications, and involving the whole society in the process.

There is thus seven chapters in the book:

- UNDERSTANDING: fundamental knowledge relevant to human health- DEVELOPING: tools for new therapies and medicines- BUILDING: tissue engineering- MODELLING: mathematical & biological models, and alternatives to animal testing- REPAIRING: preclinical & clinical studies for diseases and impairments- TREATING: improvement of standard hematopoietic stem transplantation- INTEGRATING: ethics, legal & societal aspects, training

From basic research to society: organisation of the projects in the catalogue

Organising the projects by their relevance to tissues, organs and diseases

As we appreciate that some people, in particular patients and medical doctors, can also be interested by a more clinical-oriented classification of the projects, we have added at the end of the book a list of projects per type of tissue (following their embryological origin). We also listed the projects concerning cancers and rare diseases.

In the pdf version of the book, this cross-cutting classification is a second way of accessing the projects through the bookmarks. Indeed, in addition to the table of content listing all the projects according to the research process, a second table of content lists the projects following this clinical approach, with clickable links to the projects.

UNDERSTANDING

Fundamental knowledge relevant to human health

5

CELLS INTO ORGANS: FUNCTIONAL GENOMICSFOR DEVELOPMENT AND DISEASE OF MESODERMAL ORGAN SYSTEMS

Proposal acronym CELLS INTO ORGANS EC contribution (€) 7.200.000Contract n° LSHM-CT-2004-504468 Instrument NoEDuration (starting date) 5 years (01.04.04) Participants 12

Abstract:

The development of new approaches to treating disease will revolutionise health care in the coming decade. Treatmentof cancers will increasingly rely on targeted molecules rather than cytotoxic drugs. Manipulation of stem cells for cell andtissue replacement therapies holds great promise for treatment of degenerative disease and injury. Both approachesdepend critically on detailed knowledge of the molecular and cellular events governing normal differentiation of the targetorgans and tissues. This knowledge provides the basis for organ and tissue engineering. Many important diseases affectorgan systems –such as heart, vascular system, blood, kidneys, skeleton, and musculature- deriving substantially orexclusively from mesodermal cells. Heart failure and strokes resulting from atherosclerosis, kidney failure, musculardystrophy, osteoporosis, tumours and leukaemia are caused either by defects in development of these mesodermcontaining organ systems or in their function, frequently as a consequence of ageing. Together, these diseasesrepresent principal obstacles to reaching a healthy old age. This is a very important area of research where there is agreat need to integrate resources. The area suffers from fragmentation. Different subjects are isolated Differentexperimental systems, each useful for a particular limited spectrum of experimental approaches have led to different andsometimes conflicting views. Few groups access the possibilities offered by combining approaches in differentexperimental organisms and few have attempted to integrate findings made in different species using differenttechniques. While some groups have developed important technology with potentially wide applicability or have accessto powerful resources, the technology and resources are not widely applied but usually used only by a small circle. Thisapplies notably to the recent advent of high throughput techniques and availability of related facilities like microarrays.Fourth, too few scientists think in a multi-problem, multi- system or multitechnical way. This indicates the need to train anew generation of young researchers. The primary purpose of this network is to develop an integrated approach toresearch into mesodermal organ systems. This network will elucidate molecular and cellular processes underlyingspecification and differentiation of mesodermally derived organ systems. It integrates developmental genetics andexperimental embryology with modern cell biology and genome scale analysis. These new technologies will enable toidentify genes which function in building a specific organ or in a particular aspect of embryogenesis. A major revelation ofdevelopmental biology has been the extent to which molecular strategies are redeployed, even during regeneration.Thus this information is the basic knowledge required for organ and tissue engineering. It is, however, a task which willfar exceed the capacity or expertise of any one research group, and which requires the complementary advantages ofdifferent vertebrate and invertebrate systems and the combination of multidisciplinary skills, necessitating collaboration.This network integrates twenty four leading European groups in twelve renowned centres of excellence into the world'sleading network for investigating the development and disease of mesodermal organ systems. Each of our major groupsis a world leader in investigating a specific aspect of the development of mesoderm or a key mesodermal organ systemor in applying a key genomic technique.

Web site: http://www.cellsintoorgans.net

Participants:

Coordinator

Netherlands

Profs. Anthony John Durston, Jacqueline Deschamps & Rik Korswagen, Hubrecht Laboratory /Netherlands Institute for Developmental Biology , Utrechttel: +31 30 2121 800 / 977 fax: +31 30 2516 [email protected]

Austria• Erwin Wagner & Christine Hartmann, Research Institute of Molecular Pathology, Vienna

France• Margaret Buckingham & Jean-François Nicolas, Institut Pasteur, Paris

Germany• Herbert Jaeckle, Max Planck Gesellschaft, München

Italy• Guilio Cossu, Fondazione Centro San Raffaele Del Monte Tabor, Stem Cell Res. Inst., Milan

Netherlands• Frank Grosveld, Elaine Dzierzak & Jeroen Charite, Erasmus Univ. Medical Center, Rotterdam

Portugal• Antonio Jacinto & Isabel Palmeirim-Thorsteinsdottir, Instituto Gulbenkian de Ciencia, Oieras

Switzerland• Walter Gehring & Markus Affolter, Biozentrum, University of Basel• Denis Duboule, University of Geneva, Dept of Zoology

United Kingdom• Jim Smith & John Gurdon, The Chancellor, Masters & Scholars of the University of Cambridge• Philip Ingham, Anne-Gaelle Borycki & Henry Roehl, School Med. Biomedical Sci., Univ. Sheffield• Claudio Stern & Lewis Wolpert, University College London

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases

DNA DAMAGE RESPONSE AND REPAIR MECHANISMS

Proposal acronym DNA REPAIR EC contribution (€) 11.500.000Contract n° LSHG-CT-2005-512113 Instrument IPDuration (starting date) 4 Years (01.05.05) Participants 16

Abstract:

This integrated project focuses on unravelling mechanisms of DNA damage response and repair, an area with a majorimpact on human health, notably cancer, immunodeficiency, other ageing related- diseases and inborn disorders. Theproposal brings together leading groups with multi-disciplinary and complementary expertise to cover all pathwaysimpinging upon genome stability, ranging from molecules to mouse models and human disease. Objectives: The mainobjective is to obtain an integrated perception of the individual mechanisms, their complex interplay and biologicalimpact, using approaches ranging from structural biology to systems biology. Translation of the results that we obtain isexpected to contribute to an improved quality of life through (1) possible identification of genetic markers for assessmentof susceptibility to occupational hazards and disease, (2) discovery of promising targets for therapy, (3) improveddiagnostic and prognostic procedures for genetic disorders, (4) early diagnosis and prevention of cancer and otherageing-related diseases. We have also included a strong training component in the project to invest in young talentedstudents, who may become the leaders of tomorrow. Approach: The pleiotropic effects inherent to the time-dependenterosion of the genome and the complexity of the cellular responses to DNA damage necessitate a comprehensive, multi-disciplinary approach, which ranges from molecule to patient. At the level of structural biology and biochemistry,individual components and pathways will be analysed to identify new components and clarify reaction mechanisms. Theinterplay between pathways and cross-talk with other cellular processes will be explored using both biochemical andcellular assays. To better understand the function and impact of DNA damage response and repair systems in livingorganisms, we will take full advantage of our existing unique and extensive collection of models.

Web site: http://www.erasmusmc.nl/dna-repair

Participants:

Coordinator

Netherlands

Prof. Jan H.J. Hoeijmakers, Erasmus Medical Center Rotterdamtel: +31 104 087 199 fax: +31 104 088 [email protected]

Denmark• Jiri Bartek, Danish Cancer Society, Copenhagen

France• Jean-Marc Egly, Centre Europeen pour la Recherche en Biologie et Medecine, Illkrich

Germany• Karl-Peter Hopfner, Ludwig-Maximilians-Universitat Munchen

Ireland• Noel F. Lowndes, National university of Ireland, Galway

Italy• Marco Foiani, IFOM, Istituto FIRC di Oncologia Molecolare, Milan• Paolo Plevani, Universita degli Studi di Milano, Milan

Netherlands• Leon Mullenders, Leiden University Medical Center, Division 5, Leiden

Norway• Hans Einar Krokan, Norwegian University of Science and Technology, Trondheim• Erling C. Seeberg, University of Oslo, Rikshospitalet, Oslo

Switzerland• Josef Jiricny, University of Zurich

United Kingdom• Stephen Philip Jackson, The Chancellor, Masters and Scholars of the University of Cambridge• Alan Robert Lehmann, University of Sussex, Falmer, Brighton• Stephen West, Cancer Research UK, London• Graeme Cameron Murray Smith, KuDOS Pharmaceutical Limited, Cambridge, SME

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

EMBRYOMICS: RECONSTRUCTING IN SPACE AND TIMETHE CELL LINEAGE TREE

Proposal acronym EMBRYOMICS EC contribution (€) 1.449.850Contract n° FP6-2003-NEST-B1-012916 Instrument NEST-ADVENTUREDuration (starting date) 3 years (01.11.05) Participants 4

Abstract:

Embryomics is devoted to the morphodynamical “reconstruction” of the cell lineage tree underlying the processes ofanimal embryogenesis. We will design a set of strategies, methods and algorithms to “sequence” the cell lineage tree asa branching process annotated in space and time. We view this highly interdisciplinary project as the foundation of a newscientific field that we call Embryomics with a reference to Genomics. In the same sense as Genomics, Embryomics isboth a scientific field and a technology to gather data with a lot of potential applications. But the Embryomics data ismuch more ‘complex’ than a mere DNA sequence as it does not appear as a linear static information in one dimensionbut as a branching dynamical process displayed in space and time. To deal with this information, we undertake a highlynovel and most promising approach based on the strategies of the mammalian visual system. Our goal is to fullyreconstruct the dynamics of cell divisions and movements from time-lapse series of high-resolution optical sectionsobtained by multiphoton laser scanning microscopy throughout embryonic development of live animals. Embryomics willallow the automated tracking of events such as cell division and cell death in live embryos and give us access toparameters such as the rate of cell proliferation in time and space. This kind of data is highly relevant to investigate stemcell populations, early steps of cancerogenesis and drug effects in vivo. The post-genomic era needs such a systematicapproach at the level of the cellular organization to achieve an integrated understanding of biological processes. Inaddition, through the investigation of four different organisms with key phylogenetic positions, we aim at promoting theuse of non-mammalian animal models. A comparative Embryomics strategy is the best way to evaluate the relevance ofanimal models, whatever their evolutionary distance to human, for further medical applications.

Web site: http://complexsystems.lri.fr/Embryomics/tiki-index.php

Participants:

Coordinator

France

Dr. Nadine Peyriéras, CNRS / UPR2297, Development Evolution Plasticity of the NervousSystem, Institut de Neurobiologie Alfred Fessard, Gif-sur-YvetteProf. Paul Bourgine, CNRS / Ecole Polytechnique UMR7656, Centre Research in AppliedEpistemology, Paristel: +33 1 44 32 39 55 fax: +33 1 44 32 39 [email protected]

France• Jean-François Nicolas, Molecular Biology Development Unit, Institut Pasteur, Paris

Italy• Alessandro Sarti, Department of Electronics, Information and Systems, University of Bologna

Slovakia• Karol Mikula, Department of Mathematics and Descriptive Geometry / Faculty of Civil

Engineering, Slovak University of Technology, Bratislava

Commission: Directorate General for Research - Idea programme Directorate - Unit S2

ROLE OF P63 AND RELATED PATHWAYS INEPITHELIAL STEM CELL PROLIFERATION AND DIFFERENTIATION

AND IN RARE EEC-RELATED SYNDROMES

Proposal acronym EPISTEM EC contribution (€) 2.500.000Contract n° LSHB-CT-2005-019067 Instrument IPDuration (starting date) 4 years (01.01.06) Participants 10

Abstract:

The focus of EPISTEM is to generate new knowledge and translate it into applications that enhance human health. To thisend both fundamental and applied research will be involved. `EPISTEM? integrates multidisciplinary and coordinatedefforts to understand the molecular basis of factors involved in epidermal stem cell generation, maintenance anddifferentiation and skin disease. Moreover, the core molecule that will be studied in this IP is p63 (and related pathways),a molecule genetically proven to be involved in the development of rare skin diseases such as EEC syndrome, Hay-Wells(AEC) syndrome, Limb-mammary syndrome, ADULT syndrome, Rapp-Hodgkin syndrome and non-syndromic split hand-split foot malformation. Collectively, the prevalence of ectodermal dysplasia syndromes (EDS) is estimated at 7 cases in10,000 births. Currently there is no cure for these patients. By creating the `EPISTEM? consortium we want to addressfrom different angles (genetics, gene profiling, molecular and cellular biology, structural biology, drug desing), themolecular pathways involved in epidermal dysplasia syndromes making use of different technologies (mutation analysis,micro-array, ChiP, transgenes, proteomics, in vitro skin cultures, crystallography, etc). Our consortium brings togetherleading European clinicians, geneticists, molecular and cellular biologists, structural biologists and a drug designer in thefield of p63 (and related molecules) research. Therefore, this research fits in the centre of the specific topic "Exploring thepotential of stem cells and/or primary cells for the understanding of monogenic rare diseases and the development of newdrugs for their treatments".

Web site: http://www.epistem.eu/

Participants:

Coordinator

Belgium

Prof. Peter Vandenabeele, Department for Molecular Biomedical Research, Faculty of Sciences,VIB-University Ghent, Flanders Interuniversity Institute for Biotechnology VZW, Gent-Zwijnaardetel: +32 (0) 9 33 13 760 fax: +32 (0)9 33 13 [email protected]

France• Daniel Aberdam, U634, Institut National de la Sante et de la Recherche Medicale, Nice

Germany• Volker Dötsch, Institute for Biophysical Chemistry, J. W. Goethe-Universität Frankfurt am Main,

Frankfurt / Main

Italy• Roberto Mantovani, Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi

di Milano, Milano• Alessandro Terrinoni, Biochemistry Laboratory, IDI Farmaceutici SrL, Rome, Pomezia• Gerry Melino, Biochemistry laboratory, University of Rome Tor Vergata

Department of Experimental Medicine and Biochemical Sciences, Rome, SME

Netherlands• Hans van Bokhoven, Div. Molecular Genetics, Dept. of Human Genetics, Univ. Medical Centre

Nijmegen, Stichting Katholieke Universiteit, the University Medical Centre Nijmegen, Nijmegen

Sweden• Klas Wiman, Dept. of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet,

Stockholm

Switzerland• Gian-Paolo Dotto, Department of Biochemistry, University of Lausanne, Epalinges, Lausanne

United Kingdom• John McGrath, King's College London, Genetic Skin Disease Group, King's College London,

London

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

PLATFORMS FOR BIOMEDICAL DISCOVERY WITH HUMAN ES CELLS

Proposal acronym ESTOOLS EC contribution (€) 12.000.000Contract n° LSHG-CT-2006-018739 Instrument IPDuration (starting date) 5 years (01.05.2006) Participants 18

Abstract:

The pluripotent nature of human embryonic stem (hES) cells presents unprecedented opportunities for studying humancellular differentiation and pathogenesis. Furthermore, hES cells offer a new resource for cellular transplantation in humandegenerative disease and a powerful platform for pharmaceutical and toxicology screening. The promise of hES cellsrests largely on achieving two things: (i) unlimited expansion in stem cell numbers without genetic or epigeneticcompromise; (ii) directing differentiation with absolute phenotypic fidelity. Delivery of these twin objectives entails fullunderstanding of the mechanisms that control the choices between proliferation and self renewal on the one hand, andapoptosis and commitment to differentiation on the other. Genetic intervention will be a central tool in delineating themolecular circuitry of hES cells. The goal of ESTOOLS is to develop and implement the necessary tools to elucidate thegenetic and molecular networks that control the self renewal, commitment and terminal differentiation of hES cells. Neuralcommitment provides a paradigm for understanding the mechanisms by which ES cells choose between self renewal andlineage commitment. Furthermore, neuronal and glial differentiation of hES cells offer major new experimental avenues forcellular neurobiology and pathogenesis, with the potential for application in pharmaceutical and toxicological screeningand cell replacement therapies. ESTOOLS draws together a team of high quality researchers with complementaryexpertise in mouse ES cell systems, human ES cell culture, epigenetics, neurodevelopment, and a range of geneticmodification technologies. ESTOOLS will create a range of training opportunities and dissemination vehicles to transferknowledge and experience within the European Research Area.

Web site: not yet

Participants:

Coordinator

United Kingdom

Prof. Peter Walter Andrews, Department of Biomedical Science, University of Sheffieldtel: +44-114-2224173 fax: [email protected]

Czech Republic• Petr Dvorak, Department of Molecular Embryology, Institute of Experimental Medicine, Academy

of Sciences of the Czech Republic, Brno

Finland• Timo Otonkoski, Faculty of Medicine, Developmental and Reproductive Biology Research

Program, Helsingin yliopisto, University of Helsinki• Riitta Lahesmaa, Turku Centre for Biotechnology, University of Turku

Germany• Francis Stewart, Biotec, Genomics, University of Technology Dresden, Dresden• Oliver Brüstle, Institute of Reconstructive Neurobiology, Bonn Medical Center, Rheinische

Friedrich Wilhelms Universität Bonn, Rheinische Friedrich Wilhelms Universität Bonn

Israel• Dan Pines, stem cell technologies ltd., Jerusalem, SME• Nissim Benvenisty, The Alexander Silberman Institute of Life Sciences, Faculty of Science, The

Hebrew University of Jerusalem

Italy• Elena Cattaneo, Department of Pharmacological Sciences and Center of Excellence on

Neurodegenerative Diseases, Faculty of Pharmacy, Universita' degli Studi di Milano, Milan

Netherlands• Maarten van Lohuizen, Division of Molecular Genetics, The Netherlands Cancer Institute, The

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam

Spain• Manel Esteller, Molecular Pathology Programme, Spanish National Cancer Centre, Cancer

Epigenetics Laboratory, Fundación Centro Nacional de Investigaciones Oncológicas Carlos III,Madrid

Sweden• Göran Hermerén, Department of Medical Ethics, Faculty of Medicine, Lund University, Lund• Outi Hovatti, Karolinska Institutet, Karolinska Institutet, Stockholm

Switzerland• Yves-Alain Barde, Pharmacology/Neurobiology, Biozentrum, University of Basel

United Kingdom• Paul Gerskowitch, Department of Biomedical Science, Axordia Ltd, Sheffield, SME• Austin Gerard Smith, MRC Centre Development in Stem Cell Biology, Institute for Stem Cell

Research, The University of Edinburgh• Timothy E. Allsopp, Stem Cell Sciences UK Ltd, Edinburgh, SME• Tariq Enver, MRC Molecular Haematology Unit, Medical Research Council, Headington, Oxford


THE EUROPEAN MOUSE GENOME MUTAGENESIS PROGRAM

Proposal acronym EUCOMM EC contribution (€) 13.000.000Contract n° LSHM-CT-2005-018931 Instrument IPDuration (starting date) 3 years (01.01.06) Participants 11

Abstract:

The EUCOMM integrated project responds to the priority topic defined by Priority 1. Life Sciences and Biotechnology forHealth, ?Genome-wide Mutagenesis in Mouse?. EUCOMM integrates European skills, efforts, resources, andinfrastructure to produce, in a systematic high throughput way, mutations throughout the mouse genome. A collection ofup to 20000 mutated genes will be generated in mouse embryonic stem (ES) cells using conditional gene trapping andgene targeting approaches. This library will enable mouse mutants to be established worldwide in a standardized andcost-effective manner, making mouse mutants available to a much wider biomedical research community than has beenpossible previously. For a subset of genes believed to be relevant for human disease, mutant mice will be established,archived and analyzed. This will offer an opportunity to decipher molecular disease mechanisms and in some casesprovide a foundation for the development of diagnostic, prognostic and therapeutic strategies. This project is built onexceptionally strong European expertise in mouse molecular genetics, genomics and bioinformatics and involves an SMEwhich will enable automation of targeting vector production. EUCOMM will foster integration with existing Europeanconsortia which address mouse gene expression analysis, mutant phenotyping, imaging and archiving. Progress of all ofthese projects will be enhanced by the mouse mutants produced by EUCOMM. All targeting vectors, mutant ES cells,mouse resources, and Standard Operating Procedures generated by EUCOMM will be displayed to the scientificcommunity via the EUCOMM web linked database, other EU consortia databases or the Ensembl browser and distributedby a professional distribution organization. Taken together, EUCOMM will make a major contribution to the analysis ofgene function. Finally, EUCOMM resources represent major opportunities for exploitation by SMEs and thepharmaceutical industry.

Web site: http://www.eucomm.org

Participants:

Coordinator

Germany

Prof. Wolfgang Wurst, Institute of Developmental Genetics, GSF-National Research Center forEnvironment and Health, GmbH, Neuherbergtel: +49-89-31874110 fax: [email protected] & [email protected]

France• Pierre CHAMBON, Institut Clinique de la Souris, Centre Europeen de Recherche en Biologie et

Medecine - Groupement d'Interet Economique, Illkirch

Germany• Bernhard, Korn, Research, Development & Services / Compound Heidelberg, RZPD - Deutsches

Ressourcenzentrum fur Genomforschung GmbH, Heidelberg, SME• Harald von Melchner, Laboratory for Molecular Heamatology, Johann Wolfgang Goethe University

Medical School, Frankfurt am Main• Patricia Ruiz, Max Planck Institute for molecular Genetics, Department Lehrach, Max Planck

Society for the Advancement of Science, Berlin• Francis Stewart, Biotec Genomic, Technische Universitaet Dresden• Gary Stevens & Harald Kranz, Gene Bridges GmbH, Heidelberg, SME• Nadia, Rosenthal, EMBL Programme in Mouse Biology, European Molecular Biology Laboratory,

Rome / Heildelberg

Italy• Glauco Tocchini-Valentini, Consiglio Nazionale delle Ricerche - Istituto di Biologia Cellulare,

Consiglio Nazionale delle Ricerche - Istituto di Biologia Cellulare, Monterotondo Scalo

United Kingdom• Allan Bradley, Wellcome Trust Sanger Institute, Genome Research Limited, Hinxton, Cambridge• Steve Brown, MRC Mammalian Genetics Unit, Medical Research Council, Harwell, London


EUROPEAN NETWORK ON FUNCTIONAL GENOMICS OF TYPE 2 DIABETES

Proposal acronym EUGENE2 EC contribution (€) 8.000.000Contract n° LSHM-CT-2004-512013 Instrument NoEDuration (starting date) 4 Years (01.11.04) Participants 13

Abstract:

EUGENE2 is a well focused, cohesive and multidimensional effort whereby top European laboratories, together with thebiotechnology industry, are united in a collaborative scheme to achieve a critical mass and to consolidate Europe’sposition as an international leader in the field of Type 2 diabetes and its pathogenesis.With this aim in view, EUGENE2 will group and network experts in functional genomics, genomics, proteomics andbioinformatics to unravel the complex pathogenesis of Type 2 diabetes and the specific role of the skeletal muscle, fatand the liver. In practice, this will involve the dedication and the development of common research infrastructures inhuman and rodent genomics and bioinformatics combined with cohesive research efforts in proteomics, transcriptionalregulation, insulin signalling and action in the target-tissues. A concerted effort in applying functional genomicapproaches in target cells, rodents, and humans will generate information necessary to make advances in health care,pharmaceutical development and public health policies.

Web site: http://www.eugene2.com

Participants:

Coordinator

Sweden

Prof. Ulf Smith, Goteborg University, Department of Internal Medicine, Goteborgtel: +46 31 342 11 04 fax: +46 31 829 [email protected]

Denmark• Oluf Pedersen, Steno Diabetes Center, Gentofte

Finland• Markku Laakso, University of Kuopio, Department of Medicine, Kuopio

France• Emmanuel Van Obberghen, Institut National de la Sante et de la Recherche Medicale, U45, Nice• Johan Auwerx, Centre Europeen pour la Recherche en Biologie et Medecine - Groupement

d'Interet Economique, Mouse Clinic Institute, Illkirch

Germany• Hans-Ulrich Haring, Eberhard Karls Universitaet, Medizinische Klinik IV, Tubingen• Hans-Georg Joost, German Institute of Human Nutrition Potsdam-Rehbruecke, Department of

Pharmacology, Nuthetal

Italy• Giorgio Sesti, Univ. Studi Magna Graecia di Catanzaro, Dipartimento di Medicina Sperimentale e

Clinica "Gaetano Salvatore", Catanzaro• Francesco Beguinot, Univ. Napoli Federico II, Dipart. Biol. Pat. Cell. Mol., Fac. Medicine, Naples

Spain• Fatima Bosch, Universitat Autonoma de Barcelona, Center of Animal Biotechnology and Gene

Therapy (CBATEG), Bellaterra

Sweden• Juleen R. Zierath, Karolinska Institutet, Section of Integrative Physiology, Dept. of Surgical

Science, Stockholm• Nigel Levens, Biovitrum AB, Department of Biology, Stockholm, IND

United Kingdom• Stephen O'Rahilly, The Chancellor and Masters and Scholars of the University of Cambridge,

Department of Clinical Biochemistry, Cambridge


EUROPEAN RENAL GENOME PROJECT

Proposal acronym EuReGene EC contribution (€) 10.500.000Contract n° LSHG-CT-2004-005085 Instrument IPDuration (starting date) 5 Years (01.01.05) Participants 18

Abstract:

Diseases of the kidney represent a major cause of morbidity and mortality in Europe. The elderly are disproportionatelyaffected, but renal disease is also a condition that severely affects children. An estimated 4.5 Million Europeans sufferfrom renal disorders. The death rate in patients with renal failure is 20% annually. This disease burden and its challengefor our societies is the focus of this proposal. Elucidation of the human and other genomes heralds a new era inbiomedical research offering unprecedented opportunities to understand disease processes and to identify strategies toimprove health. We will embrace these opportunities and implement an interdisciplinary research program, the EuropeanRenal Genome Project (EuReGene) that integrates European excellence in research relevant to renal development,pathophysiology and genetics. Our goal is to discover genes responsible for renal development and disease, theirproteins and their actions. To achieve this goal, we have established a consortium of leading scientists, clinicians andSME partners that will focus on the development of novel technologies and discovery tools in functional genomics andtheir application to kidney research. We will rely on comparative genomic studies in many systems that provide utilitarianmodels ranging from zebrafish, to Xenopus, to mice, to rats. Our studies will be performed at different levels including thegene, the cell, the organ and the organism. Ultimately, identification of disease genes will lead to a better understandingof renal disease processes, to improved diagnosis and to new concepts in therapy. Our program will establish aparadigm for an integrated post-genomic approach to analyze renal disease-related developments that may betransferred to other organ systems or disease entities in the future.

Web site: http://www.euregene.org

Participants:

Coordinator

Germany

Prof. Thomas E. Willnow, Max-Delbruck-Centrum Molekulare Medizin, Mol. Cardiovascular Res.tel: +49 30 9406 2569 fax: +49 30 9406 [email protected]

Belgium• Olivier Devuyst, Universite catholique Louvain, UCL Medical School, Div. Nephrology, Brussels

Denmark• Erik Ilso Christensen, University of Aarhus• Anders Nykjaer, ReceptIcon Aps, Aarhus, SME

Finland• Seppo Juhani Vainio, University of Oulu

France• Andreas Schedl, Institut National de la Santé et de la Recherche Médicale U470, Nice• Corinne Antignac, Inst. Nat. Santé et Recherche Médicale U574, Necker Hospital, Paris• Pierre Verroust, Inst. Nat. Santé et Recherche Médicale U538, CHU Saint Antoine, Paris

Germany• Gregor Eichele, Max-Planck Gesellschaft zur Forderung der Wissenschaften, MPI Experimental

Endocrinology, Hanover• Thomas J. Jentsch, Zentrum fur Molekulare Neurobiologie, Universitat Hamburg• Matthias Kretzler, Ludwig-Maximilians-Universitat Munchen - Medizinische Poliklinik, Munchen

Italy• Giuseppe Remuzzi, Istituto di Ricerche Farmacologiche Mario Negri - Department of Molecular

Medicine / Laboratori Negri Bergamo / Istituto di Ricerche Farmacologiche Mario Negri, Milano

Poland• Jakub Gburek, Wroclaw Medical University

Switzerland• Andre Werner Brandli, Swiss Federal Institute of Technology of Zurich• Heini Murer, Institute of Physiology, University of Zurich

United Kingdom• Nicholas Hastie, Medical Research Council - MRC Human Genetics Unit, London• Roger Cox, Medical Research Council, MRC Mammalian Genetics Unit, Oxfordshire• Rajesh Thakker, Chancellor, Masters and Scholars of the University of Oxford, Nuffield

Department of Clinical Medicine, Oxford


NUCLEAR ENVELOPE-LINKED RARE HUMAN DISEASES:FROM MOLECULAR PATHOPHYSIOLOGY TOWARDS CLINICAL APPLICATIONS

Proposal acronym EURO-Laminopathies EC contribution (€) 2.565.000Contract n° LSHM-CT-2005-018690 Instrument STREPDuration (starting date) 3 years (01.02.06) Participants 11

Abstract:

Laminopathies are inherited human disorders, including muscular dystrophy, cardiomyopathy, lipodystrophy, insulin-resistance, diabetes, and premature aging, which are linked to mutations in genes encoding nuclear envelope proteins,such as A-type lamins (LMNA) and lamin-binding proteins (EMD, LBR, LAP2). Laminopathies are clinically manifestedafter birth, progressively develop during childhood or adolescence, and often lead to early death. Efficient therapies havebeen hampered by the lack of understanding the molecular mechanisms causing the disorders. We will test variousdisease hypotheses, identify drug targets, and screen drugs for therapeutic interventions. Structural biologists willinvestigate how disease-causing mutations in A-type lamins or in one of their prominent binding partners LAP2alpha affectatomic structure, interactions, and assembly properties of lamins, which may reduce stress resistance in patient cells.Using patient cells and animal models (mouse, C. elegans) that either lack A-type lamins or LAP2alpha, or expressdisease variants, we will test how mutations or loss of these proteins affect chromatin organization, gene expression, anddifferentiation of adult muscle- and adipose stem cells. Differentiation will be studied ex vivo in cell culture, focusing on themolecular functions of A-type lamins and LAP2alpha in differentiation-linked pathways, and in vivo in animal modelsanalyzing muscle regeneration after stress, injury, or aging. Data obtained in these systems as well as chemicalcompound screening using the zebrafish model system will identify potential drug targets and drugs for testing in animaldisease models and for potential therapeutic intervention. Furthermore, we will extend and evaluate clinical trials on thetreatment of lipodystrophy-type laminopathy patients with drugs that target the adipocyte differentiation pathway, anddevelop theranostic tests for the validation of therapies.

Web site: http://www.projects.mfpl.ac.at/euro-laminopathies

Participants:

Coordinator

Austria

Dr. Roland Foisner, Department of Medical Biochemistry, Medizinische Universität Wien, Viennatel: +43-1-4277-61680 fax: [email protected]

Austria• Brigitte Rohner, Brigitte Rohner punkt, Vienna, SME

France• Gisèle Bonne, Inserm U582, Institut de Myologie, G.H. Pitié-Salpétrière, Institut National de la

Santé et de la Recherche Médicale, Paris

Germany• Harald Herrmann, Division of Cell Biology A010, German Cancer Research Center (Deutsches

Krebsforschungszentrum), Heidelberg

Israel• Yosef Gruenbaum, Department of Genetics, The Institute of Life Sciences, Faculty of Science,

The Hebrew University of Jerusalem, Jerusalem

Italy• Elisa Gargiullo, R&D Department, DIATHEVA s.r.l., Fano, SME• Nadir Mario Maraldi, Laboratory for Cell Biology and Electron Microscopy, Istituti Ortopedici

Rizzoli, Bologna• Giuseppe Novelli, Department of Biopatologia e Diagnostica per Immagini-Sezione di Genetica,

Universita' degli Studi di Roma Tor Vergata, Rome

Switzerland• Ueli Aebi, M.E. Mueller Institute for Structural Biology (MSB), Biozentrum, University of Basel

United Kingdom• Paul, Goldsmith, DanioLabs Discovery and Development, DanioLabs Limited, Cambridge, SME• Christopher John Hutchison, Integrative Cell Biology Laboratory, School of Biological and

Biomedical Sciences, University of Durham


EUROPEAN NETWORK TO PROMOTE RESEARCH INTOUNCOMMON CANCERS IN ADULTS AND CHILDREN:

PATHOLOGY, BIOLOGY AND GENETICS OF BONE TUMOURS

Proposal acronym EuroBoNet EC contribution (€) 13.218.960Contract n° LSHC-CT-2006-018814 Instrument NoEDuration (starting date) 5 years (01.02.06) Participants 24

Abstract:

Leading trans European research groups will integrate expertise to increase and disseminate knowledge of primary bonetumours at the molecular level for development of new tools for patient care and cure. Primary bone tumours are rare,accounting ~0.2% of the cancer burden. Children and young adolescents are frequently affected. Their aggressivenesshas major impact on morbidity and mortality. Though progress has been made in pathological and genetic typing, theaetiology is largely unknown. Advances in therapeutic approaches increased survival. Significant numbers of patients(~40%) still die from disease. Within a network of experts an exchange of material, knowledge and technology is achievedto obtain statistical significant datasets, otherwise not achievable due to the rareness and the large number of sub entities(the 2002 WHO classification recognises 31 different bone tumours. A joint programme will contribute in obtainingmolecular portraits of tumours. We focus on the molecular level, which is expedient since the availability of the wealth ofinformation from the Human Genome Project. Several bone tumours occur within a hereditary syndrome, underpinningimportance of combining a tumour and clinical genetic approach. Most tumours yield a complex and as yet not tumour-specific genetic make-up. Some specific genetic events are reported, but this knowledge is not transcribed intocomprehensive understanding, nor does it give an anchoring point for designing tumour specific therapy. The WHO hasproclaimed (endorsed by EC member countries) the “Bone and Joint Decade”, to improve the health-related quality of lifefor patients with skeletal disorders. It aims to advance understanding through research improving prevention andtreatment. This is optimal done in a multi-institutional network of expertise. Patients usually do not present themselves atcentres, which necessitates spreading of knowledge from the network into the community via a joint training program.

Web site: http://www.eurobonet.org

Participants:

Coordinator

Netherlands

Prof. Pancras C.W. Hogendoorn, Leiden University Medical Center, Depart. Pathology, Leidentel: +31 71 52 66 639 fax: +31 71 52 48 [email protected]

Belgium• Ramses Forsyth, N. Goormaghtigh Institute of Pathology, Ghent• Wim Wuyts, Universiteit Antwerpen, Department of Medical Genetics, Antwerp• Raf Sciot, Katholieke Universiteit Leuven, University Hospital, Dept. of Pathology, Leuven

Denmark• Søren Daugaard, Rigshospitalet, Department of Pathology, Copenhagen

Finland• Sakari Knuutila, Helsinki University Central Hospital, Laboratory of Cytomolecular Genetics,

Division of Pathology, Helsinki

Germany• Christopher Poremba, Heinrich-Heine-University Düsseldorf, Institute of Pathology, Düsseldorf• Thomas Aigner, Friedrich-Alexander-University Erlangen-Nürnberg, Osteoarticular and Arthritis

Research, Department of Pathology, Erlangen• Horst Bürger, Westfälische Wilhelmsuniversität Münster, Gerhard-Domagk-Institut fur Pathologie,

Munster

Hungary• Miklos Szendroi, Semmelweis University Budapest, Orthopaedics Department, Budapest

Italy• Piero Picci, Istituti Ortopedici Rizzoli, Bologna• Angelo Paolo Dei Tos, Treviso Hospital, Department of Pathology, Treviso

Netherlands• Jos Joore, Pepscan Systems B.V., Lelystad, SME• Jan Schouten, MRC Holland bv, Amsterdam, SME• Pieter Hendrik Jan Riegman, Erasmus Medical Center Rotterdam

Norway• Ola Myklebost, University of Oslo, Norwegian Radium Hospital, Institute for Cancer Research,

Dept. of Tumour Biology and Institute for Molecular Bioscience, Oslo

Spain• Enrique de Alava, Laboratory of Molecular Pathology, University of Salamanca

Sweden• Fredrik Mertens, Lund University, Depart. Clinical Genetics, Institute of Laboratory Medicine, Lund

Switzerland• Pierre Mainil-Varlet, University Bern, Institute of Pathology, Osteoarticular Research Group, Bern

United Kingdom• Rob Grimer, Royal Orthopaedic Hospital, Department of Musculoskeletal Pathology, Birmingham• Nicholas Anthony Athanasou, University of Oxford, Nuffield Depart. Orthopaedic Surgery, Oxford

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases Cancer sector

ADVANCES IN HEARING SCIENCE:FROM FUNCTIONAL GENOMICS TO THERAPIES

Proposal acronym EuroHear EC contribution (€) 12.500.000Contract n° LSHG-CT-2004-512063 Instrument IPDuration (starting date) 5 Years (01.12.04) Participants 26

Abstract:

EuroHear has two closely inter-related objectives. These are (1) to provide fundamental knowledge about thedevelopment and function of the inner ear, and (2) to identify the molecular defects underlying hereditary hearingimpairments (HI), including presbycusis, one of the most frequent forms of HI. Achieving these objectives will facilitatethe development of therapies for alleviating HI. In order to address the above issues, the EuroHear project is organisedinto 4 components: 1- The identification of genes underlying sensorineural HI in humans and mice. 2- The analysis of themolecular and cellular mechanisms underlying the development and function of: • the hair bundle; • the ribbon synapsesof the hair cell and outer hair cell electromotility; • the ion channels, ion transporters and gap junction channels thatcontribute to the potassium homeostasis. 3- The standardisation, implementation and development of technologies. 4-The development of new tools for preventing and curing HI. Currently, we identify a multidisciplinary approach as thesina qua non condition for further progress in understanding the inner ear. The EuroHear consortium comprises a groupof laboratories that are world experts in a variety of hearing research fields. EuroHear is a continuation and extension ofa previous European consortium that has successively tackled early-onset, Mendelian forms of deafness and hearingloss. The success of this European consortium, which has identified half of the 37 known genes for isolated forms of HIin humans, has been due in large part to intense collaboration between human and mouse geneticists. Expectedcontributions of EuroHear include a standardisation of investigative protocols, the provision of access to large-scaleplatforms for genetics and genomic analysis, the development and diffusion of physiological and biophysical techniquesof relevance for functional investigations of the inner ear, the creation of a variety of mouse.

Web site: http://www.eurohear.org

Participants:

Coordinator

France

Prof. Christine Petit, Institut de la Sante et de la Recherche Medicale, U587, Inst. Pasteur, Paristel: +33 1 45 17 26 60 fax: +33 1 45 17 26 [email protected]

Belgium• Guy Van Camp, Universiteit Antwerpen, Department of Medical Genetics, Antwerpen

Finland• Ulla, Pirvola, University of Helsinki, lnstitute of Biotechnology, Helsingin Yliopisto

France• Mark Lathrop, Consortium National de Recherche en Genomique, Centre Nat. Genotypage, Evry• Jacques, Prost, lnstitut Curie, Division de Recherche, Paris• Jorg Hager, IntegraGen SA, Evry, SME• Marc Poirot, Affichem, Toulouse, SME• Jonathan Dando, Inserm Transfert SA, European Project Management Department, Paris

Germany• Dominik Oliver, Universitaet klinikum Freiburg, Physiologisches Institut II, Freiburg• Jonathon Howard, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden• Thomas J. Jentsch, Universitaetsklinikum, Zentrum Molekulare Neurobiologie (ZMNH), Hamburg• Christian Kubisch, Universitaet klinikum Bonn, lnstitute of Human Genetics, Bonn• Tobias Moser, Bereich Humanmedizin Georg August, Dept. of Otorhinolaryngology, Goettingen• Klaus Willecke, Institute of Genetics University of Bonn, Institute of Genetics, University of Bonn

Hungary• E. Sylvester Vizi, Institute of Experimental Medicine, Hungarian Academy of Sciences,

Department of Pharmacology, Budapest

Israel• Karen Avraham, Tel Aviv University, Dept. of Human Genetics and Molecular Medicine, Sackler

School of Medicine, Tel Aviv

Italy• Fabio Mammano, Istituto Veneto di Medicina Molecolare (VIMM), Padova

Netherlands• Cor W.R.J. Cremers, Stichting Katholieke Universiteit, University Medical Centre Nijmegen,

Otorhinolaryngology, UMCN, Catholic University Nijmegen, Nijmegen

Spain• Felipe Moreno, Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y

Cajal, Unidad de Genetica Molecular, Hospital Ramon y Cajal, Madrid

Sweden• Mats Ulfendahl, Karolinska Institutet, Dept of Clinical Neuroscience, Stockholm• Christian, Vieider, Acreo AB, MicroTechnology Department, Kista / Stockholm, SME

Tunisia• Hammadi Ayadi, Faculty Medicine Univ. Sfax, Human Molecular Genetics Laboratory, Sfax

United Kingdom• Jonathan Ashmore, University College London, Depart. of Physiology, University College London• Steve Brown, Medical Research Council, MRC Mammalian Genetics Unit, Oxfordshire• Guy Peel Richardson, University of Sussex, School of Life Sciences, Falmer, Brighton• Karen Steel, Genome Research Limited, The Wellcome Trust Sanger Institute, Cambridge


EUROPEAN MANTLE CELL LYMPHOMA NETWORK:TRANSLATIONAL DETERMINATION OF MOLECULAR PROGNOSTIC FACTORS ANDPHARMACOGENOMICS IN A EUROPEAN INTERDISCIPLINARY COLLABORATION

Proposal acronym EUROPEAN MCL NETWORK EC contribution (€) 2.493.900Contract n° LSHC-CT-2004-503351 Instrument STREPDuration (starting date) 3 years (01.07.04) Participants 17

Abstract:

Mantle cell lymphoma (MCL) is a distinct, clinically very aggressive subentity of malignant lymphoma with a mediansurvival of 3 years. However, a small subset of patients represents long-term survivors. So far, the discriminative power ofdifferent prognostic parameters has been limited and did not allow the reliable identification of the individual patient's riskprofile. Thus, a better understanding of the underlying molecular mechanisms is eagerly warranted. In the last few years,European-wide MCL networks of clinicians (European MCL Intergroup Working Party), pathologists (European MCLPathology Panel) and basic researchers (European MCL Research Network) have been established to investigate theclinical as well as molecular aspects of malignant transformation and progression in MCL. Especially, strict diagnostichistomorphological criteria have been defined; in a prospective randomized study, an intensive consolidation with highdose radiochemotherapy and subsequent autologous stem cell transplantation resulted in superior progression-free andoverall survival rates; and most interestingly, proliferation indices have been identified as the most important prognosticfactors in MCL superior to clinical parameters (IPI). Based on these extensive prerequisites and the recent developmentof innovative molecular techniques (matrix CGH, RNA array chips, RQ-PCR, proteomics), we propose a global approachto investigate innovative treatment options of MCL and evaluate new predictive (pharmacogenomics, minimal residualdisease) and prognostic molecular markers (genomic alterations, RNA/proteome profiles) in such controlled studies. Thistranslational approach of the European MCL Network will not only lead to more individualized therapeutic strategies basedon a molecular risk profile but will also finally elucidate the way to future molecular targeted treatment options in a subtypeof malignant lymphoma with an otherwise dismal clinical outcome.

Web site: http://www.lymphome.de/en/Projects/MCL

Participants:

Coordinator

Germany

Dr. Martin Dreyling & Prof. Wolfgang Hiddemann, Ludwig-Maximilians-Universität Muenchen &Univ. Munich - Department of Internal Medicine III, Munichtel: +49 897 095 2550 fax: +49 897 095 [email protected]

Czeck Republic• Marek Trneny, Kooperativni lymfomova skupina (Czeck Lymphoma Study Group), Prague

Denmark• Niels Andersen, Rigshospitalet, University Hospital Copenhagen

France• Gilles Salles, Evelyne Calle-Bouchu & Catherine Thieblemont, Universite Claude Bernard Lyon-1

& Hematology Laboratory of Centre Hospitalier Lyon-Sud, Pierre-Bénite / Lyon• Elisabeth Macintyre, UFR Necker-Enfants Malades, Universite Paris V• Vincent Ribrag, Institut Gustave Roussy, Villejuif

Germany• Christiane Pott, Reiner Siebert & Reza Parwaresch, Christian-Albrechts-Universität zu Kiel,

Tumor Genetics Group at the Institute of Human Genetics of the University Hospital of Kiel &Institute of Hematopathology and Lymph Node Registry of Kiel

• Thomas Meitinger, GSF National Research Institute for Environment and Health, Neuhenberg• German Ott & Andreas Rosenwald, Institute of Pathology, University of Würzburg• Brigitte Schlegelberger, Institute of Cell and Molecular Pathology, Medical School of Hannover• Stephan Stilgenbauer, Medizinische Fakultät, Universität Ulm

Netherlands• Philip Kluin, University Hospital Groningen• Jacobus Johannes Maria van Dongen, Erasmus University Medical Center Rotterdam• Johannes H.J.M. van Krieken, University Medical Centre Nijmegen, Stichting Katholieke

Universiteit

Poland• Jan Walewski, Polish Lymphoma Research Group, Warzawa

Spain• Jose Angel Martinez-Climent, Hospital Clinico, Center for Applied Medical Research, Pamplona• Elias Campo, Hospital Clinic Provincial de Barcelona

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases Cancer Sector

MOLECULAR CONTROL OF ERYTHROPOIESIS

Proposal acronym EURYTHRON EC contribution (€) 2.875.996Contract n° MRTN-CT-2004-005499 Instrument Marie-Curie RTNDuration (starting date) 4 years (01.11.04) Participants 7

Abstract:

Red blood cells (RBCs) mediate oxygen transport throughout the body, a function that is essential for life. RBCs arecontinuously produced via a process called erythropoiesis. Anemias (insufficient numbers of functional RBCs), caused byfailure of erythropoiesis, are a major cause of disease in the EC.The hereditary anemias constitute the most common human genetic disorders, with no effective cure yet. We propose anRTN "Molecular Control of Erythropoiesis" which will foster a multidisciplinary approach to clarify the important molecularmechanisms in normal and pathological erythropoiesis, with a view to develop novel therapies to cure the anemias. TheRTN will generate a comprehensive molecular description of mechanisms governing erythropoiesis, from specification ofhematopoietic stem cells in embryogenesis to terminal differentiation and post-mitotic maturation of red blood cels. Forthis, the RTN will use and further develop a large number of state of the art approaches in stem cell- and erythroid cellbiology, including in vitro expansion, biochemistry of receptor / signal transducer complexes and transcription factors, andepigenetics. This mechanistic knowledge obtained within the RTN will be instrumental to devise intervention strategies foranemias and other erythroid disorders (e.g. dysplasias and leukemias). The RTN aims to (a) provide an internationaltraining platform for young scientists, (b) integrate European top-level genomics-oriented research in the area ofhematopoietic disorders, and (c) serve as a link to industrial partners, with a view to enhance the career perspectives ofyoung scientists in the European Research Area.

Web site: http://www.eurythron.org

Participants:

Coordinator

Netherlands

Dr. Sjaak Philipsen (Cell Biology), Erasmus Universitair Medisch Centrum, Rotterdamalso: Elaine Dzierzak & Frank Grosveld (Cell Biology) & Marieke von Lindern (Hematology),Erasmus MC, Rotterdamtel: +31-10-4088282 fax: [email protected]

Austria• Hartmut Beug, Institute of Molecular Pathology, Vienna

France• Paul-Henri Romeo, Patrick Mayeux & Claire Francastel, Institut Cochin, Haematology

Department, Paris

Italy• Anna Rita Migliacioo, Istituto Superiore Sanità, Rome

Netherlands• Gerald de Haan, Depart. Stem Cell Biology, Fac. Medical sciences, University of Groningen

Portugal• Maria Carmo Fonseca, Laboratory of cell biology, Institute of Molecular Medicine, Lisbon

United Kingdom• Doug Higgs,Tariq Enver & Roger Patient, Weatherall Institute of Molecular Medicine, Oxford

Commission: Directorate General for Research - Human ressources and Mobility Directorate - Marie Curie Actions

EUROPEAN TRANSCRIPTOME, REGULOMEAND CELLULAR COMMITMENT CONSORTIUM

Proposal acronym EuTRACC EC contribution (€) 9.600.000Contract n° LSHG-CT-2006-037445 Instrument IPDuration (starting date) 4 years (01.01.07) Participants 18

Abstract:

The EuTRACC consortium proposes to determine the regulation of the genome by mapping the regulatory pathways andnetworks of transcription factors that control cellular functions. EuTRACC will be part of and work in close collaborationwith the International Regulome Consortium (IRC), an worldwide network that will address the regulation of genomefunction at a higher level by mapping the genetic regulatory nodes and networks that control the activity of embryonicstem cells and the process of differentiation to specific cell types. This Integrated Project will focus on mapping thegenetic circuitry that controls the formation of neural tissues and the blood system. The project will utilize genetics,proteomics and genomics tools in the mouse, zebrafish and xenopus model organisms.

Web site: not yet

Participants:

Coordinator

Netherlands

Prof. Frank Grosveld, Department of Cell Biology, Erasmus University Medical Center, Rotterdamtel: +31-10-4087593 fax: [email protected]

Austria• Meinrad Busslinger, Research Institute of Molecular Pathology, Research Institute of Molecular

Pathology GmbH, Vienna

Canada• Michael Rudnicki, International Regulome Consortium, Ottawa Health Research Institute, Ottawa

France• Laszlo Tora, Institut de Genetique et de Biologie Moleculaire et Cellulaire, Centre Europeen pour

Recherche en Biologie et Medecine, Groupement d'Interet Economique, Illkirch

Germany• Michael Meisterernst, Institute of Molecular Immunology, Forschungszentrum fur Umwelt und

Gesundheit, Munich, Neuherberg• Ferenc Muller, Institute of Toxicology and Genetics, Forschungszentrum Karlsruhe GmbH,

Karlsruhe• Martin Vingron, Department of Computational Biology, Max Planck Society, represented by the

Max Planck Institute for Molecular Genetics, Berlin• Thomas Werner, Genomatix Software GmbH, Munich, SME• Francis A. Stewart, Biotec, Genomics, Technische Universitat Dresden, Dresden

Italy• Roberto Di Lauro, CEINGE Biotecnologie Avanzate S.C.a r.l., Naples

Netherlands• Hermanus Theodorus Marc Timmers, Department of Physiological Chemistry - Division of

Biomedical Genetics, University Medical Centre Utrecht, Utrecht

Norway• Boris Lenhard, Bergen Center for Computational Science, Computational Biology Unit,

Universitetet i Bergen, Bergen

Switzerland• Yves-Alain Barde, Division of Pharmacology/Neurobiology, Biozentrum, University of Basel

United Kingdom• Timothy Allsopp, Stem Cell Sciences UK Ltd, Edinburgh, SME• William Skarnes, Team 107, Wellcome Trust Sanger Institute, Hinxton, Cambridge• Roger Patient, Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Medical

Research Council, Headington, Oxford, London• Jim Smith, Wellcome Trust, Cancer Research UK, Gurdon Institute, The Chancellor, Master &

Scholars of the University of Cambridge• Constanze Bonifer, Division of Experimental Haematology, School of Medicine, IMMECR,

University of Leeds, Leeds


FUNCTIONAL GENOMICS OF THE RETINA IN HEALTH AND DISEASE

Proposal acronym EVI-GENORET EC contribution (€) 10.000.000Contract n° LSHG-CT-2005-512036 Instrument IPDuration (starting date) 4 Years (01.04.05) Participants 24

Abstract:

The retina is a highly complex biological system that accommodates both numerous tissue-specific and ubiquitouslyexpressed developmental and pathologic pathways. The number of genes identified in Inherited Retinal Degenerations(IRD) has steadily increased. The commonest cause of blindness, (12.5 Million affected in Europe) Age-Related-Macular-Degeneration (ARMD), is likely to depend on both mostly unknown genetic and modifying factors. Preventingblindness from IRD and ARMD requires the understanding of the genetic and cellular interactions controlling retinaldevelopment, maintenance and function. In EVI-GENORET 24 academic and industrial partners form five interactingcomponents (phenotyping, development, genetics, therapy and functional genomics) to establish working platforms,share tools and knowledge within and outside the academic community (dissemination through patient organisations andtransfer to industrial partners). This IP, spanning from the biology of seeing to the fight against retinal blindness, willimplement an accurate clinical and molecular classification of disease, identify novel retinal genes and pathways anddefine the context dependent functions of these genes in normal and degenerating tissue. The goal of the EVI-GENORET consortium is to devise plans for the development of broad scale approaches to integrating biologicalsciences over the micro- to macro-scales. Therefore, we will employ transcriptome, proteomics, protein-interactomeanalyses, functional cellular and biochemical assays, bioinformatics and model organisms to analyse patterns of geneexpression and gene function in retinal development, normal function and degeneration. The unique knowledge base onmolecular networks thus generated will facilitate identification and validation of novel therapeutic targets, of broadinterest. Developing stem cell culture methods and new approaches to gene and drug delivery mechanisms shouldprovide novel tools for therapy after testing in this privileged organ. An effective project management is ensured by thecreation of the European Vision Institute (EVI), a EEIG devoted to fostering European Vision Research.

Web site: http://www.evi-genoret.org

Participants:

Coordinator

Belgium

Prof. Jose Alain Sahel, European Vision Institute EEIG, Brusselstel: +32 2 548 02 25 fax: +32 2 548 02 [email protected]

France• Jose Alain Sahel, Institut National de la Sante et de la Recherche Medicale, Laboratoire de

Physiopathologie Cellulaire et Moleculaire de la Retine, Paris• Pascal Dolle, Centre Europeen pour la Recherche en Biologie et Medecine, Institut de Genetique

et de Biologie Moleculaire et Cellulaire, Illkirch• Kader Thiam, Genoway, Lyon, SME• Laure Benhamou, Inserm Transfert SA, Paris

Germany• Eberhart Zrenner, Eberhard-Karls-Universitaet Tuebingen, University Eye Hospital, Tuebingen• Marius Ueffing, GSF-Forschungszentrum fur Umwelt und Gesundheit GmbH, Institute of Human

Genetics, Neuherberg• Andreas Gal, University Hospital Hamburg-Eppendorf, Institute of Human Genetics, Hamburg• Frank G Holz, University of Heidelberg, Department of Ophtalmology, Heidelberg• Frank Muller, Research Centre Juelich, Institute for Biological Information Processing, Juelich

Greece• Nicolas Anagnou, National and Kapodistrian University of Athens, School of Medicine, Laboratory

of Biology, Athens

Ireland• Peter Humphries, Trinity College Dublin (TCD), Dept. Genetics, , Ocular Genetics Unit, Dublin• Gearoid Tuohy, Genable Technologies Limited, TCD, Dublin, SME

Italy• Valeria Marigo, Fondazione Telethon, Institute of Genetics and Medicine, Naples• Angelo Luigi Vescovi, Univ. Milano Bicocca, Dipartimento di Biotecnologie e Bioscienze, Milan

Netherlands• Ronald Roepman, University Medical Centre Nijmegen / University of Nijmegen, Division

Molecular Genetics, Dept. of Human Genetics, Nijmegen

Portugal• Rui Bernardes, AIBILI - Associacio para Investigacio Biomedica e Inovacio em Luz e Imagem,

CNTM- Centro de Novas Tecnologias para a Medicina, Coimbra, SME

Spain• Carmen Ayuso, Fundacion Jimenez Diaz UTE, Department od Medical Genetics, Madrid

Sweden• Theo van Veen, Lunds Universitet, Department of Ophtalmology, Wallenberg Retina Center, Lund

Switzerland• Christian Grimm, University of Zurich, University Eye Hospital, Lab of Retinal Cell Biology, Zurich• Christina Fasser, Retina International, Zurich

United Kingdom• Shomi Bhattacharya, University College London, Inst. Ophtalmology, Dept. Mol. Genetics, London• Veronica VanHeynigen, Medical Research Council, MRC Human Genetics Unit, Edinburgh• Usha Chakravarthy, The Queen's University of Belfast, Ophtalmology and Vision Science, Belfast


FUNCTIONAL GENOMICS IN ENGINEERED ES CELLS

Proposal acronym FunGenES EC contribution (€) 8.500.000Contract n° LSHG-CT-2003-503494 Instrument IPDuration (starting date) 3 years (01.03.04) Participants 18

Abstract:

The complete sequence of a mammalian genome defines the total information content. The next major challenge is tounderstand how the information is used in subsets during development - subsets that define multipotential states (stemcells); subsets that define differentiated states; and how the transitions between these states are made (lineagecommitment). The research partnership, FunGenES, will address this challenge. FunGenES will map, using bothexpression profiling and high throughput functional screens, the subsets used in pluripotent, lineage committed andselected differentiated cell types to make an atlas of mammalian genome utilization in early development. The remarkableproperties of mouse ES cells are key to the proposal. These cells are pluripotent, can be differentiated through the threemajor developmental pathways; ecto- endo- and mesoderm, to many differentiated cell types, and can be engineered.Manipulation of mouse ES cells also presents paradigms for the development of cell therapies. To accomplish this next,major, milestone in human biology, we have assembled a team of leading academic and commercial experts in the majorpathways of ES cell differentiation, anchored by common services provided by world leaders in three technology areas.These areas are - BAC transgene engineering (for efficient production of lineage reporter and selectable lines), RNAi(esiRNA; for high throughput functional screens) and database management of expression profiling. Because theseresources are centralized, and methodologies are unified for all of FunGenES, the substantial aim to generate a functionaland expression atlas database will be accomplished efficiently. The atlas is the first goal. It will provide hypotheses fortesting with advanced functional tools. By understanding how mammalian genomic information is selectively used indevelopment, we will acquire an essential key to understanding ourselves, and our health.

Web site: http://www.fungenes.org

Participants:

Coordinator

Germany

Prof. Jürgen Hescheler, Universität Kölntel: +49 221 478 737 3 fax: +49 221 478 383 [email protected]

France• Laurent Pradier, Aventis Drug Innovation & Approval, Vitry-sur-Seine, IND• Pierre Savatier, Institut National de la Santé et de la Recherche Médicale, Lyon• Christian Dani, Centre National de la Recherche Scientifique, Nice• Annette Ringwald, ARTTIC SA, Paris

Germany• Antonis Hatzopoulos, GSF-National Research Centre for Environment and Health, Neuherberg• Matthias Austen, DeveloGen Aktiengesellschaft für entwicklungsbiologische Forschung,

Goettingen, SME• Michael Bader, Max-Delbrück-Center for Molecular Medicine, Berlin• Frank Buchholz, Max-Planck-Society, Max-Planck-Institute of Molecular Cell Biology and

Genetics, Dresden• Heinz Himmelbauer, Max-Planck-Institute of Molecular Genetics, Berlin• Francis Stewart, Technical Universität Dresden• Anna M. Wobus, IPK Gatersleben, Institute of Plant Genetics and Crop Plant Research

Greece• Androniki Kretsovali, Foundation for Research & Technology Hellas - Institute of Molecular

Biology and Biotechnology, Heraklion

Italy• Angelo Luigi Vescovi, Fondazione Centro San Raffaele del Monte Tabor, Institute for Stem Cell

Research, Milan

Portugal• Domingos Henrique, Instituto de Medicina Molecular, Lisbon

United Kingdom• Lesley Forrester, University of Edinburgh• Tim Allsopp, Stem Cell Sciences Ltd, West Lothian, SME• Melanie Welham, The University of Bath


HEART FAILURE AND REPAIR

Proposal acronym HeartRepair EC contribution (€) 11.400.000Contract n° LSHM-CT-2005-018630 Instrument STREPDuration (starting date) 4 years (01.01.06) Participants 26

Abstract:

HeartRepair uses the lessons of the embryo to answer the crucial developmental questions regarding heart muscle celldifferentiation and develop techniques aimed at harnessing stem cells and or recruiting non-damaged myocardial cellsfrom the infarcted heart to facilitate cardiac repair. Myocardial infarction is the leading cause of congestive heart failuremainly caused by excessive smoking and bad dietary habits. However, the cause of the subsequent heart failure issimple, massive cardiomyocyte necrosis which fatally perturbs heart function. However, an effective therapeutic approachis simple: replacement of damaged myocardium with viable cardiomyocytes. Recent advances in the field of stem cellreplacement therapies, specifically cardiomyocyte regeneration, gains grace as a realistic alternative for congestive heartrepair. Major publications revolve around transplantation trials carried out using either embryonic stem cells or bonemarrow derived stem cells. However, Field serious questions the current scientific approach to this research and moreimportantly if, using current techniques and knowledge, such a goal can realistically ever be reached. Realization of thisaim will only be achieved by understanding the underlying principles of cardiac muscle cell formation; the missionstatement of HeartRepair HeartRepair addresses four R&D themes: 1. Genes for heart repair and plasticity, integratingclinical knowledge based genome sequencing to identify genes involved in heart development 2. Diversification of cardiacprogenitor cells, examining the genetics of cardiac muscle cell formation by exploring the process of cardiomyogenesisand subsequent differentiation 3. Cell interaction and cardiac reprogramming, exploring the details and signals necessaryto facilitate and redirect the cardiac fibroblast cell lineage for repair recruitment 4. Cardiac rejuvenation, to developtechniques to facilitate and speed repair of damaged, not yet necrotic, myocardium.

Web site: http://www.heartrepair.eu

Participants:

Coordinator

Netherlands

Prof. Antoon F. Moorman, Depart Anatomy & Embryology, Academic Medical Centre, Amsterdamtel: +31 205664928 fax: +31 [email protected]

France• Robert George Kelly, Laboratoire de Génétique et Physiologie du Développement, Institut de

Biologie du Développement de Marseille, Marseille• Margaret Elizabeth Buckingham, Génétique Mol. du Développement, Institut Pasteur, Paris

Germany• Andreas Kispert, Institut fuer Molekularbiologie, Medizinische Hochschule Hannover, Hannover• Stefanie Dimmeler, Molecular Cardiology, University of Frankfurt, Frankfurt• Silke Sperling, Cardiovascular Genetics, Max Planck Society, Max Planck Institute for Molecular

Genetics, Berlin• Ulrike Bauer, Competenz Network, Kompetenz Angeborene Herzfehler, Berlin

Italy• Marina Campione, Institute of Neurosciences, National Research Council, Padova• Giulio Cossu, Stem Cell Research Institute, DIBIT, Istituto Scientifico San Raffaele, Fondazione

Centro San Raffaele del Monte Tabor, Milan• Nadia Rosenthal, Mouse Biology Programme, EMBL, Monterotondo Scalo• Stefano Schiaffino, Dipart. Scienze Biomediche Sperimentali, Univ. degli Studi di Padova, Padova

Netherlands• Christine Mummery, Hurbrecht Laboratory, Utrecht• Maurice van den Hoff, Department of Anatomy & Embryology, Faculty of Medicine, Experimental

and Molecular Cardiology Group, Academic Medical Center, Amsterdam• Peter Abraham Christiaan 't Hoen, Human & Clinical Genetics, Leiden Univ. Med. Center, Leiden• Ingrid Kamerling, Research Department, Netherlands Heart Foundation, The Hague• Barbara JM Mulder, Depart. Cardiology, Academic Medical Center, AMC Clinical, Amsterdam• Vincent M. Christoffels, Department of Anatomy & Embryology, Faculty of Medicine, Experimental

and Molecular Cardiology Group, Academic Medical Center, Amsterdam

Spain• Diego Franco, Department of Experimental Biology, Faculty of Health and Experimental Sciences,

Cardiovascular Development Group, Universidad de Jaen, Jaen• Ramon Munoz Chapuli, Faculty of Science, Department of Animal Biology, University of Malaga• José María Pérez-Pomares, Cardiovascular Development and Angiogenesis, Depart. Biología

Animal, Facultad de Ciencias, University of Málaga & National Center of Biotechnology, Málaga

Sweden• Petter Bjorquist, Cellartis AB, Cellartis AB, Gothenburg, SME

Switzerland• Andreas Zisch, Dept. of Obstetrics, University Hospital Zurich, University of Zurich

United Kingdom• Nigel Andrew Brown, Anatomy & Developmental Biology, Saint George's Hospital Medical

School, University of London• John Burn, Inst. Human Genetics, Internat. Centre for Life, University of Newcastle upon Tyne• Judith Goodship, Institute of Human Genetics, University of Newcastle upon Tyne• Wolfgang Huber, European Bioinformatics Institute, EMBL, Cambridge


GENE NETWORKS IN CORTICAL INTERNEURON DEVELOPMENT:MODELING INTERNEURON FUNCTION IN HEALTH AND DISEASE

Proposal acronym INTERDEVO EC contribution (€) 2.000.000Contract n° LSHM-CT-2004-005139 Instrument STREPDuration (starting date) 3 Years (01.01.05) Participants 8

Abstract:

The neural assembly underlying the formation of functional networks in the cerebral cortex constitutes one of the mostcomplex neuronal systems in the brain. Much of this complexity arises during development through the interaction of twodistinct neuronal types, the glutamatergic projection neurons and g-aminobutyric containing (GABAergic) interneurons.Recently, interneuron dysfunction has been associated with severe neurological and psychiatric disorders (e.g. epilepsy,schizophrenia and bipolar disorder). In order to achieve true progress in the understanding of cortical development andof neurological diseases associated with cortical interneuron dysfunction, a complete account of the development of itsneuronal constituents is essential. In that sense, despite the detailed picture that is emerging about the development ofcortical projection neurons, the mechanisms underlying the development of interneurons in the cerebral cortex haveremained poorly defined. The general goal of the network is to obtain a comprehensive definition of the cellular andmolecular mechanisms controlling the development of cortical interneurons. To reach this aim, we will take amultidisciplinary approach by combining novel bioinformatic and genomics applications, cutting-edge imagingtechniques, and conventional cellular, molecular and electrophysiological methodologies. In addition, we will developnew genetic tools to engineer developmental models of cortical disorders involving interneuron deficiency. Thus,successful execution of the project will result in: i) New knowledge of the mechanisms underlying the specification,migration and terminal differentiation of cortical interneurons, and ii) Generation of new developmental models of corticaldisorders resulting from interneuron deficiency.

Web site: http://in.umh.es/interdevo

Participants:

Coordinator

Spain

Dr. Oscar Marin, Consejo Superior de Investigaciones Cientificas, Instituto de Neurociencias,Unidad de Neurobiologia del Desarrollo, San Joan d'Alacanttel: +34 91 585 5000 fax: +34 91 411 [email protected]

France• Alessandra Pierani, Centre national de la recherche scientifique, Department of Biology -

Regionalisation Nerveuse, Ecole Normale Superieure, Paris

Greece• Domna Karagogeos, Foundation for Research and Technology - Hellas, Institute of Molecular

Biology and Biotechnology, Heraklion

Italy• Michele Studer, Fondazione Telethon, Telethon Institute of Genetics and Medicine, Naples

Spain• Tamara, Maes, Oryzon Genomics Sa, Oryzon Genomics, Barcelona, SME• Oscar Marin, Universidad Miguel Hernandez, Instituto de Neurociencias, Unidad de Neurobiologia

del Desarrollo, San Joan d'Alacant• Liset Menendez de la Prida, Fundacion para la Investigacion Biomedica del Hospital Universitario

Ramon y Cajal, Dept Neurobiologia-Investigacion, Laboratory of Neuronal Circuits, Madrid

United Kingdom• Vassilis Pachnis & Peter Somogyi, Medical Research Council, MRC - National Institute for

Medical Research (NIMR), Division of Molecular Neurobiology, London


GENOME-WIDE DISCOVERY AND FUNCTIONAL ANALYSIS OFNOVEL GENES IN LYMPHANGIOGENESIS

Proposal acronym LYMPHANGIOGENOMICS EC contribution (€) 9.000.000Contract n° LSHG-CT-2003-503573 Instrument IPDuration (starting date) 5 years (01.05.04) Participants 13

Abstract:

The lymphatic vasculature is essential for the maintenance of fluid balance in the body, for immune defence and for theuptake of dietary fat. Absent or damaged lymphatic vessels can lead to lymphedema, a chronic and disfiguring swelling ofthe extremities, sometimes necessitating amputation of the affected limb. In addition, lymphatic vessels promotemetastatic spread of cancer cells to distant organs - a leading cause of death in patients with cancer, and a majorobstacle in the design of effective therapies. The lymphatic vessels were identified hundreds of years ago, yet very limitedunderstanding exists of their development, function and molecular mechanisms underlying their disease processes. Theaim of this proposal is to discover novel genes important for lymphatic vascular versus blood vascular development andfunction and to study the functional role and therapeutic potential of their gene products in lymphangiogenesis using state-of-the art technologies. The methods we plan to use include large-scale knockout and knock-down of the mouse genome,the embryonic stem (ES) technology, knock-down of the zebra fish genes by morpholino-antisense and positional cloningof disease susceptibility genes involved in lymphangiogenesis. These studies will provide fundamental new understandingof the molecular and cellular basis of lymphangiogenesis and therefore enable scientists to develop therapies to suppressthe growth of lymphatic vessels (eg. for cancer, inflammatory diseases) or to stimulate their growth (eg. for tissueischemia, lymphedema). The proposed Integrated Project puts forward ambitious, competitive research objectivesaddressing biological processes of high medical importance using a multidisciplinary analysis and validation approach.The participants including three European SMEs will also work according to an agreed exploitation plan for the selectedtargets.

Web site: http://www.lymphomic.org

Participants:

Coordinator

Finland

Kari Alitalo, University of Helsinkitel: +35 8 919 125 511 fax: +35 8 919 125 [email protected]

Austria• Dontscho Kerjaschki, Medical University of Vienn

Belgium• Miikka Vikkula, Christian de Duve Institute of Cellular Pathology, Brussels• Peter Carmeliet, Flanders Interuniversity Institute for Biotechnology VIB, Leuven

Finland• Seppo Yla-Herttuala, University of Kuopio• Jyrki Ingman, Lymphatix Oy (Lymphatix Ltd), Helsinki, SME

France• Anne Eichmann, Institut national de la santé et de la recherche médicale, Paris

Germany• Hellmut Augustin, KTB Tumorforschungsgesellschaft mbH, Freiburg

Italy• Elisabetta Dejana, Fondazione Italiana per la Ricerca sul Cancro, Milano

Sweden• Christer Betsholtz, Goteborg University• Lena Claesson-Welsh, Uppsala University• Mats Hellström, AngioGenetics Sweden AB, Goteborg, SME

Switzerland• Gerhard Christofori, University of Basel


MIGRATING CANCER STEM CELLS IN BREAST AND COLON CANCER

Proposal acronym MCSCs EC contribution (€) 2.150.068Contract n° LSHC-CT-2006-037603 Instrument STREPDuration (starting date) 3 years (01.11.06) Participants 5

Abstract:

Although cancer stem cells (CSC) have received much attention in the recent scientific literature, they are still defined bytheir self-renewal capability, a feature that on its own does not encompass other essential characteristics of these cells,e.g. their capacity to detach and migrate away from the primary site and invade distal organs. This operational definition ofthe migrating cancer stem cell (MCSC) is integral to another feature of neoplastic diseases, namely tumour heterogeneity.CSCs give rise to differentiated cells by asymmetric division thus providing a reservoir of multipotent descendantstogether with proliferating but progressively differentiating cells. Recent experimental evidences point out that cancer stemcells are key factors not only in local invasion and distant metastasis but also in the development of drug resistance, thusrepresenting the target for novel strategies towards tailor-made cancer therapies.The increasing knowledge of the structure and regulation of the mouse and human genomes together with the awarenessthat migrating cancer stem cell could be the ultimate target for effective therapies offer unprecedented researchopportunities.This proposal is designed to seize these opportunities and is focused on understanding the function, regulation andevolution of MCSCs in a multicellular organism. To this end we plan to identify and isolate breast and colon MCSCs bytaking advantage of unique reagents, animal models, and technical approaches, and translate the results on largecollections of human cancers, disseminating cancer cells, and metastases. The ultimate goal is to describe andfunctionally analyse the MCSCs and their micro-environment (the MCSC niche) and define a 'MCSC signature',instrumental for the development of future tailor-made therapeutic approaches.

Web site: not yet

Participants:

Coordinator

Netherlands

Prof. Riccardo Fodde, Josephine Nefkens Institute, Dept. of Pathology, Erasmus UniversityMedical Center Rotterdam, Rotterdamtel: +31 10 4087896 fax: +31 10 [email protected]

Germany• Thomas Brabletz, Laboratory of Molecular Pathology, Department of Pathology, University of

Erlangen, Erlangen• Christoph Klein, Institut für Immunologie Ludwig-Maximilians Universität München, Institut für

Immunologie Ludwig-Maximilians Universität München, München

Italy• Alberto Bardelli, Laboratory of Molecular Genetics, The Oncogenomics Center, University of

Torino School of Medicine, Fondazione Piemontese per la Ricerca sul Cancro - ONLUS -Amministrazione Ricerca, Institute for Cancer Research and Treatment, Candiolo - Torino

Spain• Manel Esteller, Molecular Pathology Programme / Spanish National Cancer Centre (CNIO) /

Cancer Epigenetics Laboratory, Spanish National Cancer Centre, Madrid


MYELOMA STEM CELL NETWORK. A TRANSLATIONAL PROGRAMMEIDENTIFYING AND TARGETING THE EARLY MYELOMA CELL HIERARCHY

Proposal acronym MSCNET EC contribution (€) 2.740.000Contract n° LSHC-CT-2006-037602 Instrument STREPDuration (starting date) 3 years (01.11.06) Participants 9

Abstract:

Multiple myeloma is an incurable disease of malignant plasma cells which accumulate in the bone marrow, for whichnovel and effective therapeutic approaches are vital. The European Myeloma Network (EMN) has recently been set up toinvestigate this disease, which may serve as a paradigm for incurable cancers. It is our belief that by defining themyeloma stem cell (MSC), this will accelerate our search for a cure for this debilitating disease. Our proposals in pursuit ofthese aims are based on 3 integrated goals:1. To establish a structural network with secure funding to underpin our co-ordinated research activities.2. To formulate a scientific framework to define the MSC and its relationship to the tumor microenvironment.3. To utilize insight from our scientific investigations to devise therapy, including immunotherapy.For Goal 1, the EMN has set out to interweave European expertise, which is at the forefront of MM research asdemonstrated by the high quality of research publications.For Goal 2, the MSCNET has delineated key strengths and limitations in the current state of the art. We will set out anumbrella strategy to examine the key issues relating to the MM stem cell, introducing novel technologies to do so.For Goal 3, it is clearly vital to define the stem or `feeder' cell in MM if the disease is to brought under long-term control orfor curative treatment. This remains a pivotal question which will dictate future development of targeted therapy.

Web site: not yet

Participants:

Coordinator

Denmark

Prof. Hans Erik Johnsen, Depart. Haematology, Aalborg Hospital, University of Aarhus, Aalborgtel: +45 99 32 68 75 fax: +45 99 32 68 [email protected]

Austria• Niklas Zojer, Wilhelminenkrebsforschungsinstitut des Österreichischen Forums gegen Krebs,

Zentrum für Onkologie und Hämatologie, Wilhelminenspital, Vienna, SME

Belgium• Karin Vanderkerken, Department of Hematology and Immunology, Faculty of Medicine, Vrije

Universiteit Brussel, Brussels

France• Bernard Klein, Unit for cellular therapy, institute of research in biotherapy and INSERM, University

of Montpellier

Germany• Friedrich W. Cremer, Myeloma Research Laboratory, Subdepartment Multiple Myeloma, Medical

Department V (Hematology and Oncology), University of Heidelberg

Netherlands• Pieter P. Sonneveld, Hematology, Erasmus Medical Center and Erasmus University, Rotterdam• Nicolaas A. Bos, Dept Cell Biology, Immunology Section, University Medical Center Groningen,

Groningen

Spain• Alberto Orfao, Department of Medicine, Faculty of Medicine and Cancer Research Center,

University of Salamanca, Salamanca

United Kingdom• Surinder Singh Sahota, Molecular Immunology Group, Tenovus Laboratory, Cancer Sciences

Division, School of Medicine, University of Southampton, Southampton


INTEGRATED FUNCTIONAL GENOMICS IN MUTANT MOUSE MODELS AS TOOLSTO INVESTIGATE THE COMPLEXITY OF HUMAN IMMUNOLOGICAL DISEASE

Proposal acronym MUGEN EC contribution (€) 11.000.000Contract n° LSHG-CT-2005-005203 Instrument NoEDuration (starting date) 5 Years (01.01.05) Participants 24

Abstract:

MUGEN aims, to structure and shape a world-class network of European scientific and technological excellence in thefield of 'murine models of human immunological diseases', to advance understanding of the genetic basis of disease andto enhance innovation and translatability of research efforts. MUGEN's specific mission is to bring together differentexpertise from academic and industrial laboratories in order to study human immunological disease by integrating theparticipant's strengths in immunological knowledge with new approaches in functional genomics. In this way MUGENexpects to bring Europe a competitive advantage in the development of new diagnostic and therapeutic tools. In concert,MUGEN will promote training of young researchers and exploitation, dissemination and communication of scientific andtechnological excellence both within and outside of the network, to include all interested stakeholders in the area ofhuman immunological diseases. Instrumental to the realization of these objectives is MUGEN's strong and coherentmanagement framework, which employs a solid organizational infrastructure, and introduces novel network supportinstruments to achieve effective decision-making and planning. With all these activities, MUGEN will make a significantcontribution to the establishment of the European Research Area and to Innovation.

Web site: http://www.mugen-noe.org

Participants:

Coordinator

Greece

Dr George Kollias, Biomedical Sciences Research Center "Alexander Fleming", Vari-Athenstel: +30 210 965 6507 fax: +30 210 965 [email protected]

Denmark• Jesper Zeuthen, Biomedical Venture, Bankinvest Group, Copenhagen, SME

France• James Di Santo, Institut Pasteur, Paris• Bernard Malissen, Centre National de la Recherche Scientifique - Delegation Provence, Marseille• Francois Romagne, Innate Pharma Sas, Marseille, SME

Germany• Werner Muller, German Research Centre for Biotechnology, Braunschweig• Manolis Pasparakis & Alvis Brazma, European Molecular Biology Laboratory, Heidelberg• Klaus Pfeffer, Heinrich-Heine-Universitat Duesseldorf, Dusseldorf• Andreas Radbruch, Deutsches Rheuma-Forschungszentrum Berlin, SME• Gunter Hammerling, Deutsches Krebsforschungszentrum, Heidelberg

Greece• Andreas Persidis, A. Persidis & Sia O.E., Athens

Italy• Giancarlo Fantucci, University of Milano-Bicocca, Milan• Paola Ricciardi-Castagnoli, Genopolis, Milan• Alberto Mantovani, Istituto di Ricerche Farmacologiche Mario Negri, Milano• Glauco Tocchini-Valentini, Consiglio Nazionale delle Ricerche - Istituto di Biologia Cellulare,

Monterotondo Scalo

Netherlands• Anton Berns, The Netherlands Cancer Institute / Antoni van Leeuwenhoek Hospital, Amsterdam

Sweden• Rikard Holmdahl, Lunds Universitet, Lund• Bjorn Lowenadler, Arexis Ab, Molndal, SME

Switzerland• Maries Van Den Broek, Inst. of Exp. Immunology, University of Zurich• Antonio Lanzavecchia, Institute for Research in Biomedicine, Bellinzona• Jurg Tschopp, University of Lausanne, Epalinges• Martin Bachmann, Cytos Biotechnology Ag, Zurich-Schlieren, SME

United Kingdom• Lars Fugger, Medical Research Council, London

United States• Klaus Rajewsky, The CBR Institute for Biomedical Research, Inc., Boston


MULTI-ORGANISMIC APPROACH TO STUDY NORMAL AND ABERRANT MUSCLEDEVELOPMENT, FUNCTION AND REPAIR

Proposal acronym MYORES EC contribution (€) 12.000.000Contract n° LSHG-CT-2004-511978 Instrument NoEDuration (starting date) 5 years (01.01.05) Participants 23

Abstract:

In Europe over 300.000 people are affected by muscular dystrophies whilst the majority of the aged population areaffected by muscle degeneration leading to decreased mobility and loss of independence. This has severe consequencesat both a personal and economic level. The aim of this proposal is to understand how these muscular defects can berepaired. Thus, the proposed project will restructure European research and will: i) integrate internationally recognisedEuropean specialists working on various aspects of muscle biology and pathology in a number of model organisms; ii)federate their research on well defined aims and obtain a critical mass of researchers who will be able to make significantscientific advancements; iii) create state-of-the-art technical platforms and resources which will serve the network'sscientific aims; iv) organize the rapid transfer and application of knowledge acquired in genetically amenable organismsinto specific applications for human muscle diseases; v) broadly publicize our scientific action and, through education,attract younger generation of scientists into this essential field of research. All aspects of muscle differentiation are to beinvestigated and this will be translated into the mechanisms of repair in the adult. Fundamental to the advancement of ourknowledge is the recent demonstration that, throughout evolution, many of the molecular mechanisms regulating muscledifferentiation have been highly conserved. As molecular pathways can be easily assessed in invertebrates, we will exploitthis advantage and rapidly extend the knowledge gained in these systems to determine gene function in highervertebrates. This is a unique aspect of the proposal and places the consortium at the international forefront ofunderstanding of gene function during normal muscle development and disease.

Web site: http://www.myores.org

Participants:

Coordinator

France

Dr. Krzysztof Jagla, Institut National de la Sante et de la Recherche Medicale, INSERM U84,Clermont-Ferrandtel: +33 4 73 17 81 81 fax: +33 4 73 27 61 [email protected]

Czech Republic• Tomas Soukup, Institute of Physiology, Academy of Sciences of the Czech Republic, IPASCR,

Department of Functional Morphology, Prague

France• Christophe Marcelle, Centre National de la Recherche Scientifique, UMR6545, Marseille• Margaret Buckingham, Institut Pasteur, Departement de Biologie du Developpement, Paris• Bernard Thisse, Institut de Genetique et de Biologie Moleculaire et Cellulaire, Illkirch• Vincent Mouly, Univ. Pierre & Marie Curie, UMR 7000, Cytosquelette et Developpement, Paris• Jonathan Dando, INSERM Transfert SA, European project management department, Paris

Germany• Beate Brand-Saberi, Univ. Klinikum Freiburg, Med. Fak., lnstitut Anatomie Zellbiologie ll, Freiburg• Ellen Furlong, European Molecular Biology Laboratory, Developmental Biology and Gene

Expression Programmes, Heidelberg• Hans-Henning Arnold, Technical University Braunschweig, Cell-and Molecular Biology,

Biosciences, Biochemistry and Biotechnology, Braunschweig• Renate Renkawitz-Pohl, Philipps-Univ. Marburg, Developmental Biology, Dep. Biology, Marburg• Carmen Birchmeier, Max-Delbruck-Centrum fur Molekulare Medizin, Berlin• Thomas Braun, Max Planck Gesellschaft, Max Planck Inst., W.G. Kerckhoff-Institut Bad Nauheim

Israel• Chaya Kalcheim, The Hebrew University of Jerusalem, Dept. of Anatomy and Cell Biology,

Faculty of Medicine, Jerusalem

Italy• Stefano Schiaffino, Univ. Studi di Padova, Dipartimento di Scienze Biomediche Sperimentali,

Padova

Spain• Alberto Ferrus, Consejo Superior de Investigaciones Cientificas, Instituto Cajal, Madrid

United Kingdom• Philip lngham, Univ. Sheffield, Centre Developm. Genetics, Dep. Biomedical Science, Sheffield• Baldjinder Mankoo, King's College London, Randall Centre For Molecular Cell Biology, London• Andrea Munsterberg, University of East Anglia, School of Biological Sciences, Cell and

Developmental Biology, UEA, Norwich• Michael Taylor, University of Wales, Cardiff, Cardiff School of Biosciences, Cardiff• John Squire, Imperial College of Science Technology & Medicine, Imperial College London• John Sparrow, The University of York, Department of Biology (Area 10), University of York• Peter Rigby, The Institute of Cancer Research : Royal Cancer Hospital, London


CANCER STEM CELLS AND ASYMMETRIC DIVISION

Proposal acronym ONCASYM EC contribution (€) 2.820.000Contract n° LSHC-CT-2006-037398 Instrument STREPDuration (starting date) 3 years (01.10.06) Participants 8

Abstract:

An intense line of current investigation in cancer is based on the connection between tumorigenesis and stem cell biology.Some tumors may originate from the transformation of normal stem cells at least in the case of blood, breast, skin, brain,spino-cerebellar and colon cancers. In addition, tumors may contain 'cancer stem cells¿, rare cells with indefinite potentialfor self-renewal, that drive tumorigenesis. Interestingly, the same signaling pathways (TGF-beta/BMP, Wnt and Notchpathways) appear to regulate self-renewal in stem cells and cancer cells.Self-renewal occurs through the asymmetric cell division of stem cells, which thereby generate a daughter stem cell andanother daughter cell that contributes to populate the developing organ or the growing tumor. In the Drosophila nervoussystem, one of the best understood asymmetric cell division models, asymmetry is mediated by a biased Notch-dependent signaling event between the two daughter cells. ONCASYM Partners have recently showed i) that the processof biased signaling during asymmetric cell division is controlled by endocytosis and ii) that tumors can be induced inmutants with altered stem-cell asymmetric division. In human normal and cancer stem cells, asymmetric cell division issupposed to take place, but it has not directly been proved yet. Furthermore, the role of biased signaling by endocytosis inthese stem cells has not been addressed to date.The aim of this proposal is 3-fold: i) to screen for genes involved in asymmetric cell division of human cancer stem cells, ii)to characterize the asymmetric cell division of these stem cells by using these candidate genes as markers anddeveloping novel specific biosensors and iii) to functionally study the role of the identified candidate genes duringasymmetric cell division of cancer stem cells. Our ultimate goal is to untangle the molecular machinery of cancer stem cellasymmetric division thereby providing drugable targets for cancer therapy.

Web site: not yet

Participants:

Coordinator

Germany

Marcos Antonio Gonzalez-Gaitan, Max Planck Institute of Molecular Cell Biology and Genetics,Gonzalez-Gaitan Lab, Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.represented by the Max Planck Institute of Molecular Cell Biology and Genetics, Dresdentel: +49 351 2102539 fax: +49 351 [email protected]

Austria• Juergen Knoblich, Institute of Molecular Biotechnology of the Austrian Academy of Sciences,

Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna

Belgium• Richard Janssen, Target Discovery, Galapagos NV, Leiden, Mechelen, IND

Germany• Carsten Schultz, Gene Expression Programme, Bioorganic Chemistry Lab, European Molecular

Biology Laboratory, Heidelberg

Italy• Pier Paolo Di Fiore, IFOM Fondazione Istituto FIRC di Oncologia Molecolare, IFOM Fondazione

Istituto FIRC di Oncologia Molecolare, Milan• Umberto Veronesi, Scientific Director's Office, Istituto Europeo di Oncologia Srl, Milan

Netherlands• Hans Clevers, Hubrecht Laboratory, Hubrecht Laboratory/KNAW, Utrecht

Spain• Cayetano Gonzalez, Institut de Recerca Biomedica - IRB, Department of Cell Division, Institut de

Recerca Biomedica, Barcelona


PLATFORMS FOR BIOMEDICAL DISCOVERY WITH HUMAN ES CELLS

Proposal acronym Plurigenes EC contribution (€) 2.500.000Contract n° LSHG-CT-2005-018673 Instrument STREPDuration (starting date) 3 years (01.01.06) Participants 8

Abstract:

A first step to regenerative medicine is to find a means to cause controlled de-differentiation of adult tissue. Plurigenesaims at achieving major breakthroughs in the discovery and understanding of the function of genes controllingpluripotency in the central nervous system. These later could enable the de-differentiation of terminally differentiatedneural cells into pluripotent cells through transgenesis, a goal that fully meets the requirements of LSH-2004-1.1.0-1.Plurigenes will start by identifying candidate genes in model organisms, following original approaches involving screensperformed by in situ hybridations on well characterised neural structures or by gain of function analysis. As pointed out inLSH-2004-1.1.0-1, innovative technologies of transgenesis and imaging in several model organisms will be settled toreach this goal. The project will first characterise in vitro and in vivo the functions of candidate genes involved in themaintenance of pluripotency. On selected genes, it will then validate the possibility to restore the pluripotency of terminallydifferentiated cells through transgenesis of the candidate genes. Finally, Plurigenes will identify molecular partners andrelated pathways associated with pluripotency. The project will result in the identification of evolutionarily conserved genesassociated with cellular pluripotency; improved methods for transgenesis in fish and ascidians and innovative methods forcell imaging and finally, protocols for the de-differentiation of neural cells.

Web site: http://www.plurigenes.org

Participants:

Coordinator

France

Dr. Jean-Stéphane Joly, Institut de Neurosciences A. Fessard, INRA U1126 "Morphogenèse dusystème nerveux des Chordés" & UPR 2197 DEPSN, CNRS, Institut National de la RechercheAgronomique, Gif-sur-Yvettetel: +33 1 69 82 34 31 fax: +33 1 69 82 34 [email protected]

France• Patrick Lemaire, LGPD, IBDM UMR6545 CNRS, Université de la Méditerranée, Centre National

de la Recherche Scientifique, Marseille• Philippe Genne, Oncodesign, Dijon, SME

Germany• Joachim Wittbrodt, Developmental Biology Programme, European Molecular Biology Laboratory,

Heidelberg• Manfred Schartl, Physiological Chemistry I, University of Wuerzburg, Wuerzburg

Italy• Filomena Ristoratore, Biochemical & Molecular Biology Laboratory, Stazione Zoologica "Anton

Dohrn", Napoli• Angelo Luigi Vescovi, Dipartimento di Biotecnologie e Bioscienze BTBS, University of Milano

Bicocca, Milan

United Kingdom• Francois Guillemot, National Institute for Medical Research, Division of Molecular Neurobiology,

Medical Research Council, London


ADVANCED GENOMICS INSTRUMENTS, TECHNOLOGY AND METHODS FORDETERMINATION OF TRANSCRIPTION FACTOR BINDING SPECIFICITIES;

APPLICATIONS FOR IDENTIFICATION OF GENESPREDISPOSING TO COLORECTAL CANCER

Proposal acronym REGULATORY GENOMICS EC contribution (€) 2.200.000Contract n° LSHG-CT-2004-512142 Instrument STREPDuration (starting date) 4 Years (01.09.04) Participants 5

Abstract:

Determination of the sequence of the human genome, and knowledge of the genetic code through which mRNA istranslated have allowed rapid progress in identification of mammalian proteins. However, less is known about themolecular mechanisms that control expression of human genes, and about the variations in gene expression thatunderlie many pathological states, including cancer. This is caused in part by lack of information about the 'secondgenetic code' - binding specificities of transcription factors (TFs). Deciphering this regulatory code is critical for cancerresearch, as little is known about the mechanisms by which the known genetic defects induce the transcriptionalprograms that control cell proliferation, survival and angiogenesis. In addition, changes in binding of transcription factorscaused by single nucleotide polymorphisms (SNPs) are likely to be a major factor in many quantitative trait conditions,including familial predisposition to cancer. We aim to develop novel genomics tools and methods for determination oftranscription factor binding specificity. These tools will be used for identification of regulatory SNPs that predispose tocolorectal cancer, and for characterization of downstream target genes that are common to multiple oncogenic TFs.Specific aims: 1. To develop novel high throughput multiwell-plate and DNA-chip based methods for determination of TFbinding specificity; 2. To experimentally determine the binding specificities of known cancer-associated TFs; 3. Tocomputationally predict, and to experimentally verify, elements that are regulated by these TFs in genes that areessential for cell proliferation; 4. To develop a SNP genotyping chip composed of SNPs that affect the function of TF-binding sites conserved in mammalian species; 5.To use this chip for genotyping of patients with hereditary cancerpredisposition as well as controls in three European populations, for identification of regulatory SNPs associated withcancer.

Web site: http://research.med.helsinki.fi/regulatorygenomics

Participants:

Coordinator

Finland

Dr. Jussi Taipale, Helsingin yliopisto, Faculty of Medicine, Molecular & Cancer Biology ResearchProgram, University of Helsinkitel: +358-9-19125556 fax: [email protected]

Denmark• Torben Falck, Orntoft, Aarhus University Hospital, Skejby, Molecular Diagnostic Laboratory,

Department of Clinical Biochemistry, Clinical Institute , Aarhus

Germany• Joerg Hoheisel, Deutsches Krebsforschungszentrum, Functional Genome Analysis, Heidelberg• Markus Beier, Magnet 41. VV GmbH, Mannheim, SME

Poland• Jan Lubinski, Pomeranian Medical University, International Hereditary Cancer Centre, Szczecin


SILENCING RNAS: ORGANISERS AND COORDINATORS OF COMPLEXITYIN EUKARYOTIC ORGANISMS

Proposal acronym SIROCCO EC contribution (€) 11.781.445Contract n° LSHG-CT-2006-037900 Instrument IPDuration (starting date) 4 years (01.01.07) Participants 18

Abstract:

A recently discovered layer of gene regulation in eukaryotic organisms employs small regulatory RNAs (miRNAs andsiRNAs). These RNAs are 20-28 nucleotides long and are produced by Dicer ribonucleases acting on double-strandedRNA precursors. Together with an effector protein complex, they scan for complementary RNA or DNA so that expressionof these targeted molecules is silenced at the transcriptional or posttranscriptional levels. These short RNAs influencegene expression during growth and development and initiate epigenetic changes to DNA and chromatin. SIROCCO willcharacterize the full complement of miRNAs and siRNAs in animals and plants. Using bioinformatics, genomics,biochemistry, cell biology and genetics, the consortium members will reveal how these RNAs are produced andprocessed, how they are transported and how they target specific genes and RNAs for silencing. SIROCCO willinvestigate the miRNA and siRNA profiles associated with development, with phenotypic divergence within populations,and with diseased states including cancer. The functional genomics of silencing RNAs will be addressed by up- or down-regulation of miRNA and siRNA species. There will also be an assessment of miRNA and siRNA regulatory networks andtheir interaction with other cellular control mechanisms. The outputs of SIROCCO will include databases of silencing RNAsequence and function in several organisms, new technologies for detection and manipulation of these RNAs, andinformation that will allow siRNA and miRNA profiles to be used as molecular markers and diagnostic methods for naturalbiological variation including the perturbations associated with disease. SIROCCO will also identify potential targets ofdisease therapy amongst the components of the small RNA silencing systems. Finally, insights generated in SIROCCOwill improve the specificity with which small RNAs can be employed as therapeutic tools.

Web site: http://www.sirocco-project.eu

Participants:

Coordinator

United Kingdom

Prof. David Baulcombe, The Sainsbury Laboratory, Norwichtel: +44 1603 450326 fax: +44 1603 [email protected]

Denmark• Jorgen Kjems, Department of Molecular Biology, University of Aarhus• Peter Mouritzen, Exiqon A/S, Vedbaek, SME

France• Annick Harel-Bellan, CNRS UPR 9079, Oncogenese, Differenciation et Transduction du Signal,

Centre National de la Recherche Scientifique, Villejuif, Paris

Germany• Michael Wassenegger, Epigenetics, RLP AgroScience GmbH, AlPlanta-Institute for Plant

Research, Neustadt• Detlef Weigel, Department of Molecular Biology, Max Planck Institute for Developmental Biology,

Max-Planck-Gesellschaft zur Forderung der Wissenschaften e.V., Tubingen, Munchen• Stephen Cohen, Developmental Biology Programme, European Molecular Biology Laboratory,

Heidelberg

Hungary• Jozsef Burgyan, Institute of Plant Biology, Molecular Virology Group, Agricultural Biotechnology

Center, Godollo

Israel• Zvi Bentwich, Rosetta Genomics Ltd, Rehovot, SME

Italy• Irene Bozzoni, Dipartimento di Genetica e Biologia Molecolare, RNA lab., Universita di Roma• Roberto Di Lauro, CEINGE Biotecnologie Avanzate S.C.a r.l., Naples

Netherlands• Ronald Plasterk, Hubrecht Laboratory / KNAW, Utrecht

Spain• Xavier Estivill, Genes and Disease Programme, Centre de Regulacio Genomica, Barcelona

Switzerland• Witold Filipowicz, Friedrich Miescher Institute, Novartis Forschungsstiftung, Zweigniederlassung

Friedrich Miescher Institute for Biomedical Research, Basel

United Kingdom• Eric Alexander Miska, Wellcome Trust/Cancer Research UK Gurdon Institute, The Chancellor,

Masters and Scholars of the University of Cambridge• Caroline Dean, Department of Cell and Developmental Biology, John Innes Centre, Norwich• Gyorgy Hutvagner, Division of Gene Regulation and Expression, Faculty of Life Sciences,

University of Dundee• Tamas Dalmay, School of Biological Sciences, University of East Anglia, Norwich


EPIGENETIC PLASTICITY OF THE GENOME

Proposal acronym THE EPIGENOME EC contribution (€) 12.500.000Contract n° LSHG-CT-2003-503433 Instrument NoEDuration (starting date) 5 years (01.06.04) Participants 18

Abstract:

In this 'post-genomic' era, advances in epigenetic research represent a new frontier that is predicted to yield novelinsights for gene regulation, cell differentiation, stem cell plasticity, organismal development, human diseases, cancer,infertility and aging. A central emerging concept proposes that there is an ‘epigenetic code’, which considerably extendsthe information potential of the genetic code. Thus, one genome can generate many ‘epigenomes’ as the fertilised eggprogresses through development and translates its information into a multitude of cell fates. Epigenetic research toucheson many topics of key interest to the general public, including embryonic and adult stem cells, and is anticipated to havefar-reaching implications for medicine and the understanding of the basic processes of cell fate determination. Theresulting developments will undoubtedly impact academic and industrial research communities and will form an importantknowledge base for policy makers and public bodies that contribute to the socio-economic future of our 'post-genomic'society.Europe has many world-leading laboratories in epigenetic research. This Network of Excellence (NoE) proposes to followa progressively expanding strategy. For its initial establishment, 25 teams from 18 different institutions with a provenrecord as leaders in their field, will constitute a ‘virtual core centre’ to combine their expertise and resources. Animmediate structuring role is provided by the concentration of most of these 25 teams around 8 established centres ofepigenetic research. In defining a coordinated joint programme of activities (JPA), this NoE will assimilate existingsynergies for building a structure that can feed three important needs: to advance scientific discoveries, integrateEuropean research and establish an open dialogue. To achieve these three goals, the core NoE will make ≥ 50% of thegrant available for network development and the durable shaping of a coherent European Research Area (ERA) onepigenetic research.

Web site: http://www.epigenome-noe.net

Participants:

Coordinator

Austria

Prof. Thomas Jenuwein, Research Institute for Molecular Pathology, Viennatel: +43 1 79 73 04 74 fax: +43 1 79 8 71 [email protected]

Austria• Denise Barlow, Research Center for Molecular Medicine, Vienna

France• Geneviève Almouzni, Institut Curie, Paris• Philip Avner, Institut Pasteur, Paris

Germany• Renato Paro, Ruprecht Karls-University Heidelberg• Ingrid Grummt, German Cancer Research Center, Heidelberg• Jörn Walter, Saarland Universty, Saarbrücken• Peter Becker, Ludwigs-Maximilians-University Munich• Gunter Reuter, Martin Luther-University Halle-Wittenberg, Halle (Saale)

Netherlands• Frank Grosveld, Erasmus Medical Center Rotterdam

Switzerland• Susan Grasser-Wilson, University of Geneva• Ueli Grossniklaus, University of Zurich

United Kingdom• Robin Allshire, The University of Edinburgh• Amanda Fisher, Medical Research Council, London• Bryan Turner, The University of Birmingham• Wolf Reik, Babraham Institute, Cambridge• Azim Surani, University of Cambridge• Peter Meyer, The University of Leeds


NOVEL TOOL FOR HIGH-THROUGHPUT CHARACTERIZATION OF GENOMICELEMENTS REGULATING GENE EXPRESSION IN CHORDATES

Proposal acronym TRANSCODE EC contribution (€) 1.000.000Contract n° LSHG-CT-2004-511990 Instrument STREPDuration (starting date) 3 years (01.01.05) Participants 5

Abstract:

The aim of this project is to develop open source tools enabling to identify in silico potential cis-regulatory modules, aswell as the transcription factors (TF) that bind to them. A publicly available genomic resource describing TF acrosschordate genomes, including mammals, fish and ascidians, will be developed. Based on this resource, large-scalesequence comparisons of orthologous non-coding regions of TF genes will be performed. Moreover, a comprehensive in-vitro study of DMA-binding affinity of TF proteins will be used to build novel models of TF binding sites. Thusmultidisciplinary approaches will be developed to identify the cis-regulatory regions driving TF gene expression. Thebasic steps undertaken will be: 1. Genome wide census and phylogenetic analysis of all TFs in sequenced chordategenomes. 2. Genome wide identification of Multi Species Conserved Sequences (MCSs) within orhtologous non-codingregions of chordate TFs. 3. Characterization of the activity of the identified MCSs in Ciona and zebrafish embryos,mammalian cells as well as in transgenic mice. 4. Training of a novel algorithm to predict and characterize MCSs activein various model systems. 5. Comprehensive determination of the in vitro DMA-binding specificity of all transcriptionfactors in a chordate genome. 6. Building novel bioinformatics models of TF binding sites based on complex grammarssuch as Hidden Markov Models and Stochastic Context Free Grammar. 7. Integration of all the above data into a publiclyavailable, open source bioinformatics tool that can be used either via the project website or downloaded for large-scaleprojects. This project represents a large-scale pluri-disciplinary effort to decipher the grammar of chordate regulatorysequences, and will have a strong impact by building tools and resources that will enable to devise more sophisticatedhypothesis regarding regulatory networks, especially those of TFs which are involved in fundamental biologicalprocesses.

Web site: http://www.transcode.tigem.it

Participants:

Coordinator

Italy

Dr. Elia Stupka, Fondazione Telethon, Telethon Inst. Genetics and Medicine (TIGEM), Naplestel: +390816132335 fax: [email protected]

France• Patrick Lemaire, Centre National de la Recherche Scientifique, LGPD, IBDM UMR6545, Marseille

Germany• Ferenc Muller, Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, Eggenstein-

Leopoldshafen

Italy• Graziano Pesole, Univ. Milano, Dipartimento di Scienze Biomolecolari e Biotecnologie, Milan

United Kingdom• Samuel Aparicio, University of Cambridge, Department of Oncology, Hutchison-MRC Research

Institute, Cambridge


DEVELOPING

Tools for new therapies and medicines

20

MODULATION OF THE RECRUITMENT OF THE VESSELS AND IMMUNE CELLSBY MALIGNANT TUMORS: TARGETING OF TUMOR VESSELSAND TRIGGERING OF ANTI-TUMOR DEFENSE MECHANISMS

Proposal acronym Anti-tumor targeting EC contribution (€) 2.420.000Contract n° LSHC-CT-2005-518178 Instrument STREPDuration (starting date) 3 years (01.11.05) Participants 8

Abstract:

All malignant tumors acquire the capacity for efficient recruitment of blood vessels, which are absolutely necessary fortumor growth beyond a certain size. They also frequently stimulate lymphangiogenesis supporting dissemination of tumorcells not only via the blood vasculature, but in addition via the lymphatic system leading to metastasis. Vessel growth ispromoted by sprouting angiogenesis and the homing of bone marrow progenitor cells into the tumors and tumor vessels.The extensive vascularization facilitates the invasion of cells of the innate and adaptive immune system, which howeverstay largely functionally suppressed by the tumor environment and even contribute to angiogenesis and tumor growth bycytokine and growth factor secretion.We propose in this application i) to further investigate key regulatory pathways by which tumor-secreted moleculespromote vascularization and inhibit immune cell function, ii) to develop methods to inhibit tumor growth and metastasisby blocking vessel and tumor cell growth, and iii) to achieve tumor clearance by additionally promoting activation andhoming of functional immune cells to the tumors.The project will comprise the collaboration of laboratories with complementary expertise. It will include experts in bloodvessel and lymph vessel angiogenesis, metastasis formation, progenitor cell incorporation into tumors and tumorvessels, anti-tumor defense mechanisms of the immune system and viral transduction techniques. The final goal will bethe preclinical evaluation of strategies in murine models of three of the most prevalent forms of human cancer, i.e.carcinomas of the breast, colon and prostate.The strategies to target the tumor will be based on gene, cell and immune therapy methods. They will include the use of i)adenoviruses for the expression of angiogenesis inhibitors following targeted delivery of the viruses to the tumorvasculature, ii) the genetic modification of murine embryonic and human umbilical cord/bone marrow progenitor cells andtheir directed homing into the tumor and iii) the use of genetically engineered immune cell products or the transduction ofimmune cells to activate targeting of the tumors by innate and adaptive anti-tumor defense mechanisms. We expect thatthis project will contribute to innovation on three levels. Firstly, we will gain basic additional novel knowledge on importantpathways and regulatory molecules for the recruitment of host cells to the tumors and their functional interaction with thetumor. Secondly, we will use this knowledge to test novel ways of targeting viruses and (transduced) cells to the tumors.Finally, we will evaluate whether by a combination of anti-angiogenesis therapy with directed anti-tumor immunotherapy itwould be possible not only to inhibit tumor growth, but to eradicate residual disease.

Web site: not yet

Participants:

Coordinator

Austria

Prof. Erhard Hofer, Medical University Vienna, Department of Vascular Biology and ThrombosisResearch Center for Biomolecular Medicine and Pharmacology, Viennatel: +43 142 776 2553 fax: +43 142 776 [email protected]

Austria• Karl-Heinz Preisegger, EccoCell Biotechnologie GmbH, Graz, SME

Germany• Antonis Hatzopolous, Gesellschaft für Strahlenforschung, Munic• Alexander H. Enk & Karsten Mahnke, University of Heidelberg, Depart. Dermatology, Heidelberg• Melvyn Little, Affimed Therapeutics AG, Heidelberg, SME

Israel• Ofer Mandelboim, The Hebrew University of Jerusalem, Lautenberg Center for General and

Tumor Immunology Hebrew-University-Hadassah Medical School, Jerusalem

Netherlands• Hidde Haisma, University Groningen, Department of Therapeutic Gene Modulation University

Centre of Pharmacy, Groningen

Switzerland• Michael Detmar, Swiss federal Institute of Technology, Department of Chemistry and Applied

Biosciences Institute of Pharmaceutical Sciences, Zurich


CONCERTED SAFETY & EFFICIENCY EVALUATION OF RETROVIRALTRANSGENESIS IN GENE THERAPY OF INHERITED DISEASES

Proposal acronym CONSERT EC contribution (€) 11.635.000Contract n° LSHB-CT-2004-005242 Instrument IPDuration (starting date) 4 Years (01.11.04) Participants 20

Abstract:

CONSERT will integrate leading European activities for a structured implementation of novel therapies using geneticallyenhanced postnatal stem cells, with focus on the treatment of monogenic immunodeficiencies, hemoglobinopathies,anemias and storage disorders. CONSERT will develop and evaluate methods for genetic stem cell modification withwide implications for many other disorders including viral infection and cancer. A central and exceptional theme of ourwork is an unbiased safety and efficiency evaluation of the key technology used in the genetic modifications of replicatingsomatic cells: retroviral vector-mediated transgenesis. This is only possible through concerted multi-center studies. Lenti,spuma- and gammaretroviral vectors will be tailor-made for target disorders and tested for potency and safety inpreclinical disease models. Designed with a translational aim, basic studies in stem cell biology and selectable markertechnology will complement this research. A unique and most important aspect of CONSERT is the molecular andclinical monitoring of currently active and successful clinical trials of genetic therapies. This will create a paradigmaticdata-mining activity to obtain insights into crucial issues of clonal kinetics of gene-modified cells in vivo. In parallel,molecular studies in precise cell systems and animal models will provide a deeper mechanistic understanding oftransgene-host interactions. This project will create a perfect basis for technology development and simultaneouslypromote patient safety. Translational dissemination of know-how from academia to industry will create a network of cellprocessing manufacturers with large economic potential, and prepare future clinical studies with improved predictability.Supervised by a proactive ethical project, CONSERT will stimulate a competitive and complementary evolution ofbiomedical academia, clinics, innovative health service providers, and associated training opportunities.

Web site: http://www.genetherapy.nl

Participants:

Coordinator

Netherlands

Prof. Gerard Wagemaker, Erasmus University Medical Center Rotterdam, Institute of Hematology,Rotterdamtel: +31 10 408 7766 fax: +31 10 408 [email protected]

France• Francois-Loic Cosset, Alain Fisher & Marina Cavazzana-Calvo, Institut National de la Sante et de

la Recherche Medicinale, INSERM U412 - LVRTG, Lyon & INSERM U429, Hopital Necker, Paris• Olivier Danos, Genethon, Evry, France• William Saurin, Genomining, Montrouge, SME

Germany• Christopher Baum, Medizinische Hochschule Hannover, Dept. of Hematology, Hemostaseology

and Oncology, Laboratory of Experimental Cell Therapy, Hannover• Christof von Kalle, Universitaet klinikum, Institute for Molecular Medicine and Cell Research, Stem

Cell Biology Lab, Freiburg• Klaus Kuehlcke, Europaeisches Institut fur Forschung und Entwicklung von

Transplantationsstrategie AG, Idar-Oberstein, SME• Michael Fuchs, Institut fur Wissenschaft und Ethik e.V., Section Biomedical Ethics, Bonn• Thomas M. Pohl, GATC Biotech AG, Konstanz, SME

Greece• Nicholas Anagnou & George Vassilopoulos, Univ. Athens School Medicine, Lab. Biology, Athens

Italy• Fulvio Mavilio, Molecular Medicine S.p.A., Milan, SME• Luigi Naldini, Fondazione Centro San Raffaele del Monte Tabor, DIBIT-TIGET, Milan• Maria Grazia Roncarolo, Universita Vita-Salute San Raffaele, Faculty of Medicine, Milan

Netherlands• Louise van den Bos, Science & Technology Transfer (S&TT), Rotterdam, SME

Spain• Jordi Barquinero, Centre de Transfusio i Banc de Teixits, Unitat de Diagnostic i Terapia

Molecular, Barcelona• Juan M. Bueren, Centro de Investigaciones Energeticas Mediambientales Y Technologicas,

Hematopoiesis Program, Madrid

Sweden• Stefan Karlsson, Lunds Universitet, Medical Faculty, Molecular Med. and Gene Therapy, Lund

Switzerland• Didier Trono, Univ. Geneva, Fac. Medicine, CMU, Depart. Microbiology & Mol. Med., Geneva

United Kingdom• Adrian Trasher & Mary Collins, Inst. Child Health & Univ. College London, London• Lez Fairbairn, University Manchester, Dept. of Cancer Studies, Christie Hospital, Manchester


CRYO-BANKING OF STEM CELLS FOR HUMAN THERAPEUTIC APPLICATION

Proposal acronym CRYSTAL EC contribution (€) 2.400.000Contract n° LSHB-CT-2006-037261 Instrument STREPDuration (starting date) 3 years (01.02.07) Participants 7

Abstract:

Stem cells are at the centre of biomedical research. The development of human stem cell therapies will have to build on asafe and reliable supply of human stem cells which must be assured by cell banking.Currently, the isolation, identification and culture of stem cells are not standardised between laboratories, andreproducibility of protocols is limited. Today's banking approaches still rely on storing sources of stem cells rather than onbanking of defined, well-characterised stem cell populations (both adult and embryonic). Cryopreservation of stem cellsitself is not yet optimised and validated for the different cell types, and multiple cell biological and biophysical challengesremain to be addressed in order to define optimised cryopreservation protocols.The problems currently limiting the routine application of stem cell banking with a therapeutic perspective will beaddressed by the CRYSTAL project. The consortium will develop tools and optimised procedures to enablecryopreservation of different stem cell types and allow safe production of sufficient numbers of high-quality cells for futurehuman therapy. This will comprise standardised protocols and tools for stem cell isolation, identification and culture, novelapproaches to their cryopreservation (e.g. novel cryoprotectants, freezing in different conformations) and an automatedquality control system for stem cell preparations. Five stem cell research laboratories providing four different sources ofadult (from cord blood, bone marrow and placenta) and human embryonic stem cells have teamed with two partnersspecialising in applied banking and fundamental cryobiological research. CRYSTAL is thus in a position to solve existingproblems in an integrated, systematic approach and to provide standardised, reproducible methods and tools to advancetherapeutic stem cell research in Europe.

Web site: not yet

Participants:

Coordinator

Germany

Prof. Jürgen Hescheler, Institute of Neurophysiology, University of Colognetel: +49-221-4786960 fax: [email protected] & [email protected]

Austria• Andrea Kolbus, Gynecological Endocrinology and Reproductive Medicine, Medical University of

Vienna, Department of Obstetrics and Gynecology, Vienna

Belgium• Catherine Verfaillie, Hematology Section, Katholieke Universiteit Leuven, Leuven• Peter Ponsaerts, University Hospital Anwerp, Laboratory of Experimental Hematology, University

of Antwerp, Edegem

Germany• Heiko Zimmermann, Fraunhofer-Institut für Biomedizinische Technik, St. Ingbert, München

Netherlands• Guy Wouters, Cryo-Save-Labs, Life-Sciences Group NV, Mechelen, Zutphen, SME

Switzerland• Andreas Hugo Zisch, Obstetrics, University Hospital Zurich, University Zurich


EUROPEAN EMBRYONAL TUMOR PIPELINE

Proposal acronym E.E.T.-Pipeline EC contribution (€) 4.000.000Contract n° LSHC-CT-2006-037260 Instrument STREPDuration (starting date) 3 years (01.01.07) Participants 13

Abstract:

Treatment of embryonal tumors (ET) is a challenge for the pediatric oncologist. Innovative translational research isrequired to exploit available genomic data and implement state-of-the-art technologies to overcome the deficits of currentdiagnostic and treatment strategies. We will set up a consortium of leading European institutions and SMEs with extensiveclinical and technological expertise to establish a unique pipeline for the comprehensive development and validation ofnovel diagnostic tools in addition to efficient preclinical drug development for ET.Our holistic approach includes:1) Validation of a chip-based diagnostic platform tailored specifically for ET including analysis of genes previously shownby the consortium to be affected in ET2) Generation of ET-specific data on novel array-based platforms for the development of diagnostics at the microRNA andserum proteomics levels3) Extension of an existing database designed to warehouse complete clinical and experimental data for neuroblastoma toinclude all ET entities4) Implementation of a virtual ET-Biobank to improve sharing of patient samples5) Functional characterisation of the most promising molecular targets previously identified by the partners as afoundation for entry into a drug development pipeline6) Integration of existing disease-specific mouse models to evaluate new treatment modalities in vivo7) Initial evaluation of screening methods for small molecules and antibodies affecting ET cell growth8) Application of novel bioinformatic solutions for the meta-analyses9) Dissemination of the novel tools to researchers and clinical study centers in EuropeOur coordinated effort can achieve the critical mass to facilitate the necessary integration of research capacities fortranslating ET genome data into significant medical progress. Involvement of clinical study centers will ensure a direct linkto the bedside, aimed at improving child health and quality of life.

Web site: not yet

Participants:

Coordinator

Germany

Prof. Angelika Eggert, Pediatric Oncology, University Hospital of Essentel: +49 2017233755 fax: +49 [email protected]

Austria• Heinrich Kovar, Children's Cancer Research Institute, Vienna

Belgium• Chris Roelant, Memobead Technologies, Boom, SME• Frank Speleman, Centre for Medical Genetics, Ghent University, Ghent

France• Olivier Delattre, Unite 509 Inserm, Institut Curie, Paris

Germany• Joe Lewis, Chemical Biology Core Facility, European Molecular Biology Laboratory, Heidelberg• Manfred Schwab, Tumour Genetics, German Cancer Research Center, Heidelberg• Roland Eils, Division of Theoretical Bioinformatics, German Cancer Research Center, Heidelberg

Italy• Alessandro Bulfone, bio))flag Srl, Pula, SME• Massimo Zollo, CEINGE-BIOTECNOLOGIE AVANZATE S.C. a.r.l., Naples

Norway• Björn Cochlovius, Affitech AS, Oslo, SME

Slovenia• Saso Dzeroski, Department of Knowledge Technologies, Jozef Stefan Institute, Ljubljana

Switzerland• Michael Grotzer, Department of Oncology, University Children's Hospital of Zurich


EPISOMAL VECTORS AS GENE DELIVERY SYSTEMSFOR THERAPEUTIC APPLICATION

Proposal acronym EPI-VECTOR EC contribution (€) 2.100.000Contract n° LSHB-CT-2004-511965 Instrument STREPDuration (starting date) 3 years (01.01.05) Participants 8

Abstract:

Many chronic human diseases cause great suffering as a result of inherited and sporadic genetic mutations. Gene therapyprovides therapeutic benefit if a normal copy of the affected gene can be expressed in appropriate target cells.Retroviruses are often used for gene delivery, as the therapeutic gene integrates into a host cell chromosome. Asintegration is targeted to active chromatin this ensures long-term expression. However, this can disrupt gene expressionat the integration site and lead to cancer. We propose that safe DNA vectors for human gene therapy must delivertherapeutic levels of gene expression without altering patterns of expression in the host cells. Extra-chromosomal geneexpression vectors provide the best way of achieving this. Results will provide novel DNA vectors and protocols that willbe used as gene delivery systems for therapeutic application. Expression vectors will be developed using rational designparameters that incorporate existing knowledge of genetic and epigenetic factors that regulate chromatin function inmammalian cells. DNA vectors will be designed specifically for ectopie gene expression from extra-chromosomal loci inthe host cells, to provide regulated gene expression for safe, efficient and sustained gene therapy. Extra-chromosomalgene expression vectors will be validated for human gene therapy in a pre-clinical setting and protocols for clinicalapplication established. Prototype extra-chromosomal gene expression systems that provide efficient and sustained geneexpression will be refined to develop second-generation gene therapy vectors. We will use a systematic analysis ofgenetic elements to define design parameters for rational vector construction. The performance of second-generationgene expression vectors will be validated for human gene therapy in a pre-clinical setting and protocols for clinicalapplication will be established using myocytes, hepatocytes and haemotopoeitic stems cells as model systems.

Web site: http://www.ls.manchester.ac.uk/epivector

Participants:

Coordinator

United Kingdom

Dr. Dean A. Jackson & Dr. Anne-Marie Buckle, Faculty of Life Sciences, University of Manchestertel: +44 1612 004 255 +44 161 306 4214 fax: +44 1612 360 [email protected] [email protected]

Germany• Hans Joachim Lipps, University of Witten, Institute for Cell Biology, Witten• Juergen Bode, GBF, German Research Center for Biotechnology, Braunschweig• Ben Davies, GenOway GmbH, Hamburg, SME

Israel• Ariella Oppenheim, The Hebrew University of Jerusalem, Dept. of Hematology, Hebrew

University-Hadassah Medical School, Jerusalem

Netherlands• Roeland Van Driel, Univ. Amsterdam, Swammerdam Institute for Life Sciences, Amsterdam

Spain• Fernando Azorin, Consejo Superior de Investigaciones Cientificas, Department of Molecular and

Cellular Biology - Instituto de Biologia Molecular de Barcelona

United Kingdom• John George Dickson, Royal Holloway & Bedford New College - University of London, Centre for

Biological Sciences, Egham, Surrey


NOVEL APPROACHES TO PATHOGENESIS, DIAGNOSIS AND TREATMENTOF AUTOIMMUNE DISEASES BASED ON NEW INSIGHTS

INTO THYMUS-DEPENDENT SELF-TOLERANCE

Proposal acronym EURO-THYMAIDE EC contribution (€) 12.000.000Contract n° LSHB-CT-2003-503410 Instrument IPDuration (starting date) 5 years (01.01.04) Participants 25

Abstract:

Autoimmune diseases are a significant burden for the quality of life and health care cost. Despite intense research efforts,the mechanisms underlying the development of autoimmune diseases are still largely obscure. This obvious ignoranceexplains why the current treatment of these chronic diseases remains inadequate and is associated with severe sideeffects. Here we propose an original and new approach to tackle this problem. Our approach is mainly based on the majorbiological function of the thymus, i.e. to ensure the generation of a diverse repertoire of T cell receptors that are self-tolerant. The thymus achieves this goal by using two complementary mechanisms: a) apoptotic deletion anddevelopmental arrest of T cells bearing a receptor (TCR) with high affinity for self-antigens presented by majorhistocompatibility complex (MHC) proteins expressed by thymic epithelial and dendritic cells, and b) generation of self-antigen specific regulatory T cells. The escape from central self-tolerance now appears to play a prominent role in thedevelopment of autoimmune diseases. Six workpackages will achieve the objectives of this proposal: 1. Intrathymicpromiscuous gene expression and self-peptide tolerogenic therapy. 2. Preclinical studies of the autoimmune regulator(AIRE) in gene therapy. 3. Interest of anti-Coxsackievirus B4 vaccination for prevention of type 1 diabetes. 4. Explorationof a new T cell pathway governing autoimmunity and allergy. 5. Development, function and therapeutic utility of regulatoryT cells in autoimmune diseases and asthma. 6. Evaluation of thymic epithelial stem cell therapeutic potential. Thisambitious research project will lead to new insights into disease mechanisms, and will concurrently provide a uniqueplatform for innovative diagnostics and for disease-specific therapy aimed at a cure and prevention of autoimmunediseases, such as type 1 diabetes as a prototypic target of this proposal.

Web site: http://www.eurothymaide.org

Participants:

Coordinator

Belgium

Prof. Vincent G. Geenen, University of Liegetel: +32 4 366 25 50 fax: +32 4 366 29 [email protected]

Austria• Ludger Klein, Research Institute of Molecular Pathology, Vienna• Josef Penninger, Inst. of Molecular Biotechnology of The Austria Academy of Sciences, Vienna• Josef Penninger, Apeiron Biologics, Vienna, SME

Australia• Hamish S. Scott, The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria

Belgium• Alain Bosseloir, Zentech, Angleur, SME• David Muntz, Euro Top, Brussels, SME

Canada• Rafick-Pierre Sekali, Université de Montréal

Estonia• Part Peterson, University of Tartu

Finland• Minna Valtavaara, FIT Biotech Oyj Plc, Tampere, SME

France• Philippe Naquet, Centre National De La Recherche Scientifique, Marseille• Didier Hober, Centre Hospitalier Régional et Universitaire de Lille• Joost van Meerwijk, Institut National de la Sante et de la Recherche Medicale, Toulouse

Germany• Bruno Kyewski, Deutsches Krebsforschungszentrum (German Cancer Res. Center), Heidelberg• Alexander Marx, Bayerische Julius Maximilians-Universitat Wurzburg• Thomas Boehm, Max-Planck-Society for the Advancement of Science, Max-Planck-Institute of

Immunobiology, Freiburg• Lutz Zeitlmann, Ingenium Pharmaceuticals Ag, Martinsried, SME

Italy• Isabella Screpanti, Dipartimento di Medicina Sperimentale e Patologia (DMSP) Universita Degli

Studi Di Roma - La Sapienza

Spain• Ricardo Pujol-Borrell, Lab. Immunobiology for Research and Applications to Diagnosis (LIRAD),

Institute Germans Trias & Pujol for Research in Health Sciences (IGTP), U. A. Barcelona• Dolores Jaraquemada, Laboratory of Cellular Immunology, Institut de Bioteccnologia i

Biomedicina (IBB), Universita Autonoma de Barcelona

Switzerland• Georg A. Hollander, University of Basel• Antonius Rolink, University of Basel

United Kingdom• Fiona Powrie, Chancellor Masters and Scholars of the University of Oxford• Catherine Martha Hawrylowicz, King’s College London• Eric John Jenkinson, University of Birmingham


TARGETING CANCER STEM CELLS FOR THERAPY

Proposal acronym EuroCSC EC contribution (€) 1.900.000Contract n° LSHC-CT-2006-037632 Instrument STREPDuration (starting date) 3 years (01.01.07) Participants 6

Abstract:

Cancer remains one of the leading causes of death in the Western world, and while chemotherapy has provided a majorimprovement in survival for a wide array of malignant diseases lethality remains high in most cancers and side-effects aresevere, and include developmental impairment, when used in childhood malignancies, infertility as well as damage to non-malignant tissues with resulting diminished quality of life for a large proportion of survivors. Recently, the realization thatseveral tumour types contain rare populations of cancer stem cells (CSCs), which are capable of reforming the tumourupon transplantation while their progeny are not, have opened the possibility of using CSCs as targets for directedmolecular therapies that could lead to improved tumour eradication as well as reduced side effects of treatment. The goalof the present project is to perform a thorough characterization of AML, cALL and breast cancer CSCs, as well as asystematic comparison of these with their normal stem cell and progenitor counterparts using gene profiling, to identifyputative molecular targets in CSCs. In parallel, we will use mouse genetic modelling to obtain information about genesregulated by oncogenic changes in stem- and progenitor cell populations. Directly oncoprotein-regulated CSC targets willbe validated in vitro and, where relevant, in vivo. Finally, we will screen small molecule libraries for compounds thatantagonize leukemogenic oncoproteins in efficient zebrafish models. These compounds will be tested for activity inmammalian assays, screened against the putative targets identified by gene profiling, and used to affinity-purify additionalinteracting proteins. The final outcome will be a set of identified and validated CSC molecular targets, and acorresponding collection of small molecule inhibitors with activity against the effects of leukemogenic oncoproteins onhematopoietic stem cell/progenitor populations.

Web site: not yet

Participants:

Coordinator

Germany

Dr. Claus Nerlov, Mouse Biology Unit, European Molecular Biology Laboratory, Monterotondo(Italy), Heidelbergtel: +39 06 9009 1218 fax: +39 06 9009 [email protected]

Denmark• Ole William Petersen, Structural Cell Biology Unit, Department of Anatomy, The Panum Institute,

University of Copenhagen, Copenhagen

Sweden• Sten Eirik Jacobsen, Lund Strategic Center for Stem Cell Biology and Cell Therapy, Medical

Faculty, Lunds Universitet, Lund

United Kingdom• Dominique Bonnet, Haematopoietic Stem Cell Laboratory, London Research Institute, Cancer

Research UK, London• Roger Patient, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, Medical

Research Council, Headington, London• Jon Tinsley, VASTox plc, Abingdon, SME


EUROPEAN CONSORTIUM FOR STEM CELL RESEARCH

Proposal acronym EUROSTEMCELL EC contribution (€) 11.906.400Contract n° LSHB-CT-2003-503005 Instrument IPDuration (starting date) 4 years (01.02.04) Participants 14

Abstract:

The goal of the 4-year project is to develop an advanced technological platform for new cell based therapies and create afoundation for translational research in the stem cell field. The project draws together the capabilities of 11 academiccentres and 3 industries in 8 European countries, with expertise encompassing transgenesis, stem cell biology,developmental biology, tissue repair, in vivo disease models and clinical cell transplantation. The key aim is to developwell-characterized cell lines of therapeutic potential derived from stem cells of embryonic, neural, mesodermal andepithelial origin. The breadth and scale of this project are unprecedented in the stem cell field worldwide and will enablefor the first time a systematic comparative evaluation of the properties and therapeutic potential of stem cells ofembryonic, foetal and adult origin. The research is organized in 7 Work Packages: Identification and Isolation (WP 1),Lineage Analysis and Differentiation Potential (WP 2), Self-Renewal and Upscaling (WP 3), Control of Differentiation (WP4), Application in Neurological Disease (WP 5), Muscle Repair (WP 6) and Epidermal Repair (WP 7). Spanning the workpackages are three Flagship Projects aimed at Generation of new antibody reagents against stem cells (FSP 1),development of a prototype European Stem Database and Stem Cell Repository (FSP 2), and a Forum for Ethics andSocial Issues related to stem cell research (FSP 3). A pan-European Training Program will promote interdisciplinary andtrans-European collaboration and technology transfer, and stimulate the recruitment of young scientists and clinicalresearchers to the stem cell field. Three industries are fully integrated in the programme and an IPR Management Teamwill ensure that intellectual property and commercial exploitation are professionally handled. In summary, theEuroStemCell consortium brings together the leading investigators across Europe to create a team unmatched in quality.

Web site: http://www.eurostemcell.org

Participants:

Coordinator

United Kingdom

Prof. Austin Smith, The University of Edinburgh, Scotlandtel: +44 131 650 5890 fax: +44 131 650 [email protected]

Denmark• Lars Wahlberg, NsGene A/S, Ballerup, SME

France• Margaret Buckingham, Institut Pasteur, Paris

Germany• Olivier Brüstle, University of Bonn Medical Center

Italy• Giulio Cossu, Fondazione Centro San Raffaele del Monte Tabor, Milano• Elena Cattaneo, Universita' degli Studi di Milano, Milano• Claus Nerlov, European Molecular Biology Laboratory, Monterotondo

Sweden• Anders Björklund, Lunds Universitet• Urban Lendahl, Karolinska Institutet, Stockholm• Katarina Jansson, Neuronova AB, Stockholm, SME

Switzerland• Yann Barrandon, Swiss Federal Institute of Technology Lausanne

United Kingdom• Fiona Watt, Cancer Research UK, London• John McCafferty, Genome Research Ltd, London• Timothy Allsopp, Stem Cell Sciences UK Ltd, West Lothian, SME


TARGETING NEWLY DISCOVERED OXYGEN-SENSING CASCADES FOR NOVELCANCER TREATMENTS BIOLOGY, EQUIPMENT, DRUG CANDIDATES

Proposal acronym EUROXY EC contribution (€) 8.000.000Contract n° LSHC-CT-2003-502932 Instrument IPDuration (starting date) 5 years (01.02.04) Participants 21

Abstract:

The last decade's basic and clinical oncology research has revealed a number of so far unrecognised regulatingresponses (e.g. HIF-1) in cells exposed to hypoxia. These processes have been proven highly important for tumourprogression and resistance to radiotherapy and certain types of chemotherapy. Because of their strong over-expression insolid cancer tumours in comparison to adjacent normal tissue, this new knowledge may open a therapeutic window forcancer treatment targeting hypoxia-responsive processes. Major EU stakeholders in academic research and industry willtherefore explore and validate these new molecular targets as a necessary step in the preclinical development ofinnovative new diagnostics and treatment. Our editing committee found it necessary to go over all aspects of the total taskin order to plan the initial work correctly and feel that evaluators will have the same need. We therefore present tightlystructured and fully described workpackages for all five years. Our committee has identified the outstanding basicproblems to be solved over the first 2 to 3 years in order to allow a successful drug development. These include:dissection of relevant steps in cancer cell response to hypoxia, development of the technology platform needed, andfurther identification and characterisation of marker/target molecules. Our own mid-term evaluation will then select whichhypoxic processes may be suitable as targets for cancer- specific treatment. After this, we will study diagnostic taggingand therapeutic strategies leading up to a selection process of promising compounds to be further developed. The newtreatments will be developed along two lines: targeting known cytostatics towards the newly discovered hypoxia-responsive molecules and searching for so far unused compounds, preferably toxic to pathways active during hypoxia.The final effort will be to ensure continued industry utilisation of our results.

Web site: http://www.funding.aau.dk/goingproj.htm

Participants:

Coordinator

Denmark

Prof. Peter Ebbesen, Aalborg Universitet, Laboratory for Stem Cell Research, Aarhus Ctel: +45 861 273 66 fax: +45 861 954 [email protected]

Denmark• Peter Mosborg Petersen, Vivox ApS, Aarhus, SME• Anders B. Damholt, Leo Pharma AS, Ballerup, SME

France• Marie-Christine Multon, Aventis Pharma, Vitry-sur-Seine, IND

Germany• Martina Rimmele, RiNA-Netzwerk RNA Technologien GmbH, Berlin• Alfons Krug, LEA Medizintechnik GmbH, Giessen, SME• Jobst Gerhard, Jobst Technologies GmbH, IND• Agnes Görlach, Deutsches Herzzentrum München• Kai-Uwe Eckardt, University of Erlangen-Nuremberg, Division of Nephrology and Hypertension,

Erlangen

Italy Andrea Scozzafava, University of Florence

Lithuania• Arvydas Kanopka, Institute of Biotechnology, Vilnius

Netherlands• Phillippe Lambin & Bradly Wouters, University of Maastrich Research Institute Growth and

Development (GROW), Maastricht

Norway• Erik Olai Pettersen, University of Oslo

Slovakia• Silvia Pastrorekova, Slovak Academy of Sciences, Bratislava

Sweden• Lorenz Poellinger, Karolinska Institutet, Stockholm

Switzerland• Roland Hugo Wenger, University of Zurich

United Kingdom• Ian James Stratford, The Victoria University of Manchester• Peter Ratcliffe & Adrian Harris, Chancellor Masters and Scholars of the University of Oxford,

Molecular Oncology Laboratory, Cancer Research UK, John Radcliffe Hospital, WeatherallInstitute of Molecular Medicine, Oxford

• Stuart Naylor, Oxford BioMedica Plc, SME• Patrick Maxwell, Imperial College of Sciences, London• David Blakey, AstraZeneca UK limited, London, IND


EUROPEAN VASCULAR GENOMICS NETWORK

Proposal acronym EVGN EC contribution (€) 9.000.000Contract n° LSHM-CT-2003-5023254 Instrument NoEDuration (starting date) 5 years (01.01.04) Participants 28

Abstract:

Cardiovascular diseases (CVD) caused 51% of deaths in Europe in 2001, while cancer accounted for 20%. Coronaryheart disease and stroke, which result from atherosclerosis, constitute 80% of CVD. Better prevention and treatmentshave halved age-specific incidence, but the ageing population and adverse trends in obesity and diabetes threaten theseimprovements. There is also an alarming increase in heart failure, the end stage of coronary heart disease. Futureadvances depend on developing entirely new strategies. Genomics and proteomics together complete human genomeopen up fresh horizons for molecular understanding of cardiovascular disease, for identifying new diagnosticmeasurements and developing new pharmacological, gene and cell-based therapies. The European Vascular GenomicsNetwork (EVGN) seeks to assemble the necessary critical mass and promote multidisciplinary interactions by uniting 25world-leading basic and clinical institutions from 9 European countries. It focuses on the three areas with greatesttherapeutic potential: 1) endothelial dysfunction, an early critical event in atherosclerosis and hence a target forprevention, 2) plaque instability, responsible for precipitating thrombosis and hence most life-threatening acute events,and 3) therapeutic angiogenesis either conventional or cell-based to recover ischaemic organ function and reduce heartfailure. Our research armoury spans genomics, proteomics, molecular biology, cell biology, gene transfer and geneticmodification in mice, and integrative pathophysiology in man. The EVGN will maximize the scientific and commercialpotential of European vascular biology by electronic data-sharing and communication networks, shared research tools,and exchange and training programmes. The EVGN will train tomorrow's lead investigators through a European PhD,which will also address adverse gender balance and encourage excellence in Eastern Europe, which suffers highprevalence of CVD.

Web site: http://www.evgn.org

Participants:

Coordinator

France

Dr. Alain Tedgui, Institut National de la Santé et de la Recherche Médicaletel: +33 1 44 63 18 66 fax: +33 1 42 81 31 [email protected]

Austria• Bernd Binder, Department of Vascular Biology, University of Vienna• Georg Wick, University of Innsbruck, Medical School, Institute of Pathophysiology, Innsbruck• Helga Vetr, Technoclone GmbH, Vienna, SME

Finland• Seppo Ylä-Herttuala, University of Kuopio, A.I. Virtanen Institute, Kuopio

France• Johan Auwerx, Institut Clinique de la Souris, Strasbourg• Emmanuelle Benhamou, Inserm-Transfert SA, Paris

Germany• Ingrid Fleming, Institut fur Kardiovaskulare Physiologie, University of Frankfurt• Thomas Münzel, University Hospital Eppend, Division of Cardiology, Hamburg• Georg Nickenig, Medizinische Klinik und Poliklinik, University of Saar, Homburg/Saar

Israel• Eli Keshet, Faculty of Medicine, Institute of Microbiology, The Hebrew University of Jerusalem

Italy• Elisabetta Dejana, FIRC Institute of Molecular Oncology, Milan• Attilio Maseri, San Raffaele Hospital, Cardiothoracic & Vascular Dept., Milan• Federico Bussolino, University of Torino, Dept of Oncological Sciences, Torino• Paolo Madeddu, National Institute of Biostructures and Biosystems, Experimental Medicine and

Gene Therapy, Osilo

Netherlands• Harry Struijker-Boudier, Cardiovascular Research Institute Maastricht (CARIM)• Victor van Hingsbergh, Gaubius Laboratory, Leiden• Theo van Berkel, University of Leiden, Division of Biopharmaceutics, Leiden• Hans Pannekoek, University of Amsterdam, Academic Medical Center, Amsterdam

Sweden• Goran Hansson, Karolinska Hospital, Karolinska Institutet, Stockholm

Switzerland• Thomas Lüscher, University Hospital, Cardiology, Zürich• Francois Mach, University Hospital Geneva, Cardiovascular Biology Research Unit, Geneva

United Kingdom• Andrew Newby, Bristol Heart Institute, University of Bristol• Martin Bennett, Addenbrooke's Hospital, Cardiovascular Medicine, Cambridge• Qingbo Xu, St. George's Medical School, Department of Cardiovascular Sciences, London• Asif Ahmed, School of Medicine, Reproduction and Vascular Biology, University of Birmingham• Patrick Vallance, University College London, Department of Medicine BHF Laboratories, London• John Martin, Ark Therapeutics Ltd, London, SME


GENE THERAPY: AN INTEGRATED APPROACH FOR NEOPLASTIC TREATMENT

Proposal acronym GIANT EC contribution (€) 9.700.000Contract n° LSHB-CT-2004-512087 Instrument IPDuration (starting date) 5 Years (01.01.05) Participants 14

Abstract:

Translation of genetic knowledge from the Human Genome into disease-specific therapy for untreatable congenital andacquired diseases is now reality. However, the gene therapy vectors currently used in experimental settings can bedeveloped for safe clinical application only if fundamental problems are solved: ie the limitation of vector dose byattachment targeting and expression control and a decrease of non-specific toxicity. Minimisation of vectorimmunogenicity (stealthing) is necessary to reduce bloodstream and immune-mediated reduction of effective vectorconcentration. In the GIANT project, targeting and stealthing of both viral and non-viral vectors will be used to selectcandidates for testing in Phase I clinical studies. GIANT will concentrate firstly on one uniform model system and diseasetarget (prostate carcinoma) for vector testing standardisation and in vitro, preclinical and clinical vector comparison. Wewill use a clinically approved vector backbone of adenoviral constructs re-targeted to prostate cancer via surfaceantigens, and hybrid prostate targeted promoters. The consortium includes a GMP vector production facility and clinicalfacilities with scientific and ethical permission to carry out human cytotoxic gene therapy trials, guaranteeing theimmmediate translation of selected vectors into the clinical testing. The biomaterials obtained will serve to develop newassays for vector distribution, efficacy and monitoring of the immune response against various vector systems. TheGIANT participants have a long record of EU-based scientific collaboration and expertise in ethically approved clinicalvector generation. The SMEs own international patents on retargeting vectors and target discovery methods, providing atechnology platform for further exploration of promising targets and innovative approaches to facilitate treatment ofneoplastic diseases. An external Scientific Advisory Board will be convened to oversee progress.

Web site: http://www.york.ac.uk/depts/biol/units/cru/giant

Participants:

Coordinator

United Kingdom

Prof. Norman James Maitland, Univ. York, Cancer Research Unit, Department of Biology, Yorktel: +44 1904 328700 fax: +44 1904 [email protected]

Czech Republic• Karel Ulbrich, Institute of Macromolecular Chemistry Academy of Sciences of the Czech Republic,

Department of biomedicinal polymers, Prague

France• Jean-Paul Behr, Universite Louis Pasteur, Faculte de Pharmacie, Laboratoire de Chimie

Genetique, UMR 7514, Illkirch Graffenstaden• Patrick Erbacher, Polyplus Transfection, Illkirch, SME

Germany• Stefan Kohchanek, Universitat Ulm, Division of Gene Therapy, Ulm• Ernst Wagner, Ludwig-Maximilians-Universitaet Muenchen, Department of Pharmacy, Chair

Pharmaceutical Biology - Biotechnology, Munich

Netherlands• Chris Bangma, Erasmus MC, University Medical Center, Department of Urology, Rotterdam• Rob C Hoeben, Leids Universitair Medisch Centrum, Dep. of Molecular Cell Biology, Leiden• Wytske van Weerden, Scuron B.V., Rotterdam, SME

Sweden• Thomas Totterman, Uppsala Universitet, Department of Oncology, Radiology and Clinical

Immunology / Division of Clinical Immunology, Uppsala• Leif Lindholm, Got-a-Gene AB, Gothenburg, SME

United Kingdom• Leonard Seymour, The Chancellor, Masters and Scholars of the University of Oxford, Department

of Clinical Pharmacology, Oxford• Alan Raymond, Pro-Cure Therapeutics L.t.d, York, SME• Kerry Fisher, Hybrid Systems Ltd., Oxford, SME


DEVELOPMENT AND APPLICATION OF TRANSPOSONS AND SITE-SPECIFICINTEGRATION TECHNOLOGIES AS NON-VIRAL GENE DELIVERY METHODS

FOR EX VIVO GENE-BASED THERAPIES

Proposal acronym INTHER EC contribution (€) 2.800.000Contract n° LSHB-CT-2005-018961 Instrument STREPDuration (starting date) 3 years (01.11.05) Participants 10

Abstract:

Considerable effort has been devoted to the development of gene delivery strategies for the treatment of inherited andaquired disorders in humans. Ex vivo gene therapies are based on removing cells from a patient, introducing a therapeuticgene construct into the cells, and implanting the engineered cells back into the patient. Currently, both viral and non-viralmethods are used for gene delivery. Viral vectors are efficient in gene transfer, but their use raises serious safetyconcerns. Non-viral methods are usually safer but less efficient in providing long-term therapeutic transgene expression.Transposable elements can be considered as natural, non-viral delivery vehicles capable of efficient genomic insertion. Inthis project, novel gene transfer technologies will be established by developing transposon vectors that mediate efficientand targeted integration of therapeutic genes into the genome. Therapeutic gene constructs will be made in transposonvectors, and delivered into cells ex vivo, using cutting edge non-viral nucleic acid delivery methods. Application ofreversible implantation systems (collagen implants, skin biopumps, and encapsulated cells) will be explored. Animaldisease models will include copper metabolism diseases, anemia, hypercholesterolemia, bleeding disorders, chronicgrnulomatous disease and neurological disorders. Genomic insertion, transgene expression and phenotypic correction willbe investigated. Safety issues of transposon vector administration and genomic integration will be addressed. Theinvolvement of three SMEs will mobilise industrial know-how and technology. This project will develop, test and apply newtherapeutic tools for somatic gene therapy as an alternative to currently used viral and non-viral technologies, and willhave the potential to offer new solutions for diseases that impose significant impairment to citizens? quality of life, as wellas burdens on health care services in Europe.

Web site: not yet

Participants:

Coordinator

Germany

Dr. Zsuzsanna Izsvak, Max-Delbruck-Centrum fur Molekulare Medizin, Berlintel: +49 30 9406-2546 fax: +49 30 [email protected]

Belgium• Marinee (Khim Lay) Chuah, Molecular Cardiovascular Medicine Group, Center for Transgene

Technology & Gene Therapy, VIB-University of Leuven, Flanders Interuniversity Institute forBiotechnology, Leuven

Denmark• Lars Wahlberg, Research and Development / Clinical Development, NSGene A/S, Ballerup, SME• Thomas Jensen, The Kennedy Institute-National Eye Clinic, The Kennedy Institute-National Eye

Clinic, Glostrup

Finland• Seppo Yla-Herttuala, A.I. Virtanen Institute, Department of Biotechnology and Molecular

Medicine, University of Kuopio

Germany• Herbert Müller-Hartmann, Research & Development, amaxa GmbH, Köln, SME

Hungary• Balazs Sarkadi, Department of Molecular Cell Biology, National Medical Center, Budapest• Peter Krajcsi, Solvo Biotechnology Inc., Budapest, Szeged, SME

Israel• Eithan Galun, Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Hospital,

Hadassah Medical organization, Jerusalem

Sweden• Ulo Langel, Department of Neurochemistry and Neurotoxicology, Stockholms Universitet,

Stockholm


DEVELOPING A STEM CELL BASED THERAPYTO REPLACE NEPHRONS LOST THROUGH REFLUX NEPHROPATHY

Proposal acronym KIDSTEM EC contribution (€) 2.463.000Contract n° MRTN-CT-2006-036097 Instrument Marie-Curie RTNDuration (starting date) 4 years (01.09.2006) Participants 6

Abstract:

The aim of this project is to design a stem cell-based therapy to prevent end-stage renal disease caused by refluxnephropathy in children. The two main reasons to focus on this condition are that it is the major cause of kidney failure inchildren and young adults and secondly, the disease typically takes several years to reach end stage, allowing time fortherapies to repair damaged kidneys before they become completely non-functional. Recent advances in stem cellscience and tissue engineering present an unprecedented opportunity to design a stem cell therapy for this clinicalproblem. This project will investigate the properties of several different stem cell types (embryonic stem cells, kidneystem cells, amniotic fluid stem cells and mesenchymal stem cells) in order to determine which is most appropriate for thegeneration of functional kidney tissue. To do this, novel biomaterials will be designed that will provide a substrate both forthe generation of kidney progenitor cells and for their transplantation.

Web site: http://www.kidstem.org

Participants:

Coordinator

United Kingdom

Dr. Patricia Ann Murray, School of Biological Sciences, University of Liverpool, Liverpooltel: +44 151 795 4456 fax: +44 151 794 [email protected]

Austria• Markus Hengstschlaeger, Medical University of Vienna, Vienna

Germany• C Werner, Max Bergmann Center of Biomaterials Dresden, Leibniz-Institut fur Polymerforschung

Dresden e.V., Dresden

Italy• Giovanni Gamussi, Department of Internal Medicine, Laboratory of Renal Immunopathology,

Universita' Degli Studi di Torino, Turin• Giuseppe Remuzzi, Department of Molecular Medicine / Mario Negri Institute for Pharmacological

Research, Istituto di Ricerche Farmacologiche Mario Negri, Bergamo

United Kingdom• Jamie Davies, Centre for Integrative Physiology, University of Edinburgh, Edinburgh


COMBINED ISOLATION AND STABLE NONVIRAL TRANSFECTION OFHEMATOPOIETIC CELLS ? A NOVEL PLATFORM TECHNOLOGY

FOR EX VIVO HEMATOPOIETIC STEM CELL GENE THERAPY

Proposal acronym magselectofection EC contribution (€) 2.800.000Contract n° LSHB-CT-2006-019038 Instrument STREPDuration (starting date) 4 years (01.05.06) Participants 13

Abstract:

The feasibility of ex vivo gene therapy in humans has been demonstrated with retrovirally transduced hematopoietic stemcells. At the same time, risks associated with the use of retroviral vectors became apparent. We will establish and validatea novel combination technology for hematopoietic cell isolation and nonviral transfection leading to site-specific genomicintegration of transfected nucleic acids. This novel technology will be validated by expert groups in hematopoietic stemcell gene therapy and related basic and clinical research. The technology is going to be exploited and disseminated by thecompany partners Miltenyi Biotech, OZ Biosciences, MolMed, and Poetic Genetics. A platform technology for nonviraltransfection of hematopoietic cells in general and hemaptopoietic stem cells in particular, with optional stable geneticmodification, will be established by integrating a clinically approved magnetic cell separation technique (CliniMACS) withmagnetically enhanced transfection (Magnetofection). Cell nucleus-targeting vectors will be applied. For selectedindications, the technology will be practiced with plasmid constructs that provide site-specific genomic integration, eitherthe phage phiC31 integrase system or, alternatively, a drug-inducible AAV-derived replicase/integrase system.Technology validation includes the analysis of genomic integration sites, transcriptom profiling, characterization of stableand inducible trans-gene expression and evaluation of engraftment and persistence in transgenic animal models usingmolecular biological tools and magnetic resonance imaging. The therapeutic potential will be examined in a SCID-Xmouse model in direct comparison with established retroviral technology. Magselectofection is expected to circumventproblems associated with viral vectors, contribute to health care progress and foster the competitiveness of Europe?sbiotechnology industry based on its competitive advantage.

Web site: http://magselectofection.eu

Participants:

Coordinator

Germany

Dr. Christian Plank, Institute of Experimental Oncology, Klinikum rechts der Isar der TechnischenUniversität München, Munich , 0049-89-4140-4453, 0049-89-4140-4476, [email protected]: +31 71 52 66 639 fax: +31 71 52 48 [email protected]

Austria• Peter Steinlein, BioOptics Department, Research Institute of Molecular Pathology, Vienna, IND

France• Olivier Zelphati, R&D, Oz Biosciences, Marseille, SME

Germany• Joseph Rosenecker, Department of Pediatrics, Ludwig-Maximilians-Universität, Munich• Lena Grimm, Fraunhofer Patentstelle, Fraunhofer Gesellschaft zur Förderung der angewandten

Forschung e.V., Munich• Ian Johnston, Research and Development, Miltenyi Biotech GmbH, Bergisch Gladbach, IND

Israel• Tsvee Lapidot, Department of Immunology, Weizmann Institute of Science, Rehovot

Italy• Fulvio Mavilio, Discovery, Molecular Medicine S.p.A., Milano, SME

Netherlands• Marcel Thalen, Synco Bio Partners B.V., Amsterdam, SME• Gerard Wagemaker, Hematology, Stem Cell Gene Therapy Development, Erasmus University

Medical Center, Rotterdam

Poland• Zygmunt, Pojda, Department of Experimental Hematology & Cord Blood Bank, M. Sklodowska-

Curie Memorial Cancer Center and Institute of Oncology, Warsaw

Slovakia• Melania Babincova, Department of Nuclear Physics and Biophysics, Comenius University,

Bratislava

United States• Michele P. Calos, Department of Genetics, Stanford University School of Medicine, Stanford,

California, Stanford, California


MODULAR DEVICES FOR ULTRAHIGH-THROUGHPUTAND SMALL VOLUME NUCLEOFECTION

Proposal acronym MODEST EC contribution (€) 2.755.468Contract n° LSHG-CT-2006-037291 Instrument SME-STREPDuration (starting date) 3 years (01.02.07) Participants 5

Abstract:

Modification of cells is a central topic in pharmaceutical and medical sciences as well as in basic research. Innumerableopportunities, e.g., in discovery of new regulatory pathways, novel targets, and potential drug candidates as well asclarification of signal transduction are addressed by cell transfection technology. The dominant consideration for cellmanipulation is the type of cells used. Until now, most often conventional, immortal cell lines, being cultured for years oreven decades in flasks, have been assigned to this specified use, although they are mainly irrelevant in physiological andmedical repects. The optimal choice would be primary cells, since they are distinctly closer to the physiological situationthan cell lines. Researchers would make rapid strides in the analysis of the biology of cells towards the development oftherapeutics and new types of treatments as well as possible cures for a variety of diseases and injuries would befacilitated by using primary cells instead of cell lines. However, primary cells until recently were hard or often evenimpossible to transfect by non-viral methods, and consequently, many researchers still hesitate to adopt these cellsdespite their unquestionable advantages. With the advent of the nucleofection technology, a unique method for the highlyefficient transfection of primary cells was recently made available to the life science community. With MODEST the mainobjectives are i) the development of devices for one-step, ultra high throughput nucleofection of primary cells in modularmulti-well plates, and ii) the application of this technology to the highly relevant area of immunological as well as neuronaldisorders to facilitate investigations of possible mechanisms of intervention.

Web site: not yet

Participants:

Coordinator

Germany

Dr., Birgit, Nelsen-Salz, administration, amaxa GmbH, Koeln, DE, undefined, Germany, Y, IND,PRC, +49-221-99199 148, +49-221-99199 119, [email protected]: +31 71 52 66 639 fax: +31 71 52 48 [email protected]

Estonia• Kaia Palm, Protobios Ltd., Tallinn, SME

Germany• Alexander Scheffold, Immunomodulation, Deutsches Rheuma Forschungszentrum Berlin, Berlin• Jorg Potzsch, RNAx GmbH, Berlin,

Sweden• Thomas Schaumann, Manager Life Science Sales, Teleca Sweden East AB, Stockholm


DEVELOPING MOLECULAR MEDICINES FOR CANCERIN THE POST GENOME ERA BASED ON TELOMERASE

AND RELATED TELOMERE-MAINTENANCE MECHANISMS AS TARGETS

Proposal acronym MOL CANCER MED EC contribution (€) 4.000.000Contract n° LSHC-CT-2003-502943 Instrument IPDuration (starting date) 4 years (01.10.04) Participants 14

Abstract:

Cancer is a European public health problem of overwhelming human and economic significance. There is now animproved molecular understanding of the key genetic, biochemical and cellular changes leading to cancer, in significantpart due to the efforts of diverse groups of world-class EU-based scientists. With the completion of the human genomesequence imminent, it is now timely to initiate a major European co-ordinated effort to translate fundamental scientificknowledge about cancer into safer, more effective, therapies and improved early diagnostic procedures.The cellular immortality enzyme telomerase (one of the most promising universal cancer markers) and associatedtelomere maintenance mechanisms, represent novel anti-cancer targets of enormous therapeutic and diagnosticpotential. In MOL CANCER MED, we have established a multinational EU translational cancer research consortium, inwhich talented cancer geneticists and molecular biologists will interact with prominent pharmacologists, clinicians andpathologists to develop these exciting new cellular targets into measurable pre-clinical advances, within a 4-year time-frame.The project has been structured into three, highly interactive Areas of Activity, involving the fundamental evaluation andpre-clinical validation of: (i) telomerase as a target for cancer treatment and diagnosis based on new molecular knowledgeabout its expression and function, (ii) associated downstream telomere maintenance mechanisms as additional targets fornovel drug design, and (iii) new anticancer drugs based on these targets. The Consortium will bring to bear diverse andcomplementary technological know-how of considerable power to deliver the above primary objectives. Effectivemanagement will maximize synergies across MOL CANCER MED in order to produce genuine improvements in thedesign of new treatments that promise to be active against a broad spectrum of common human malignancies.

Web site: http://www.brunel.ac.uk/about/acad/health/healthres/researchareas/bicgp/molcancermed

Participants:

Coordinator

United Kingdom

Prof. Robert F Newbold, Brunel Institute of Cancer Genetics and Pharmacogenomicstel: +44 1895 203090 fax: +44 1895 [email protected]

Denmark• Nedime Serakinci, University of Aarhus

France• Jean-Louis Mergny, Museum National d’Histoire Naturelle, INSERM U-565, Paris

Germany• Uwe Martens, University Hospital, Freiburg• Petra Boukamp, DKFZ, Heidelberg

Italy• Nadia Zaffaroni, National Cancer Institute, Milan• Maurizio D’Incalci, Instituto Mario Negri, Milan

Spain• María A. Blasco, Spanish National Cancer Centre, Madrid

Sweden• Göran Roos, Umeå University, Umeå

Switzerland• Joachim Lingner, ISREC, Lausanne

United Kingdom• W. Nicol Keith, University of Glasgow, Cancer Research UK Beatson Laboratories, Glasgow• Stephen Neidle, The School of Pharmacy, University of London, London• Eric Kenneth Parkinson, University of Glasgow, School of Veterinary Pathology• John Mann, Queens University, Belfast


AMPLIFICATION OF HUMAN MYOGENIC STEM CELLS IN CLINICAL CONDITIONS

Proposal acronym MYOAMP EC contribution (€) 2.480.000Contract n° LSHB-CT-2006-037479 Instrument SME-STREPDuration (starting date) 3 years (01.12.06) Participants 10

Abstract:

The aim of this network is to synergize expertises from European basic researchers, leaders in their field, and EuropeanSMEs specialized in stem cell amplification and in safety of these procedures, to set up conditions for autologous transferof human stem cells in GMP conditions for the treatment of DMD by exon-skipping. Cell therapy trials in DMD has neverfulfilled the promises raised by the early results obtained in mouse models. Several groups have recently demonstratedthe possibility of generating a truncated, but functional dystrophin using exon-skipping, by masking splicing sequenceswith oligonucleotides introduced by either direct or viral transfer. The direct approach can be used as many times asneeded, but is extremely expensive, while the AAV approach allows a large dissemination of the masking sequences, buttriggers an immune response to the vector, and therefore can be used only once. Cell therapy can thus be used to targetsites which have not been cured by the AAV approach, using autologous cells as vectors which, by fusing with theregenerating fibres of the patient, will bring a functional dystrophin to these fibres. Myoblasts become progressivelyexhausted in DMD patients as the disease progresses, while stem cells, such as mesoangioblasts or AC133+, remainintact and functional. However, little is known either about the possibility to transduce these cells with oligonucleotides orvectors for exon-skipping, or the methods that can be used to expand these cells in GMP conditions. The technical andethical guidelines resulting from this network will enable SMEs to expand stem cells with myogenic potential in GMPconditions for clinical trials in patients with DMD or other neuromuscular diseases. This network is a natural link betweenMYORES, an existing NoE dedicated to muscle research, and TREAT, an upcoming NoE dedicated to therapeutics (FP64th Call, line LSH-2005-2.1.1-7), since it gathers specialists belonging to both NoE.

Web site: not yet

Participants:

Coordinator

France

Dr. Gillian Butler-Browne, Stem cell and muscle biology, Institut National de la Santé et de laRecherche Médicale, Paristel: +33 1 40 77 96 36 fax: +33 1 53 60 08 [email protected]

France• Anton Ottavi, European project management department, Inserm-transfert, St Beauzire, Paris• Otto Merten, Département de Développement, Genethon, Evry, SME• Christophe Gaillard, GenoSafe SAS, Evry• Luis Garcia, Centre de recherche et d'applications sur les thérapies géniques, Centre National de

la Recherche Scientifique, Evry

Germany• Felicia M Rosenthal, Cellgenix technologie Transfer GmbH, Freiburg, SME

Italy• Yvan Torrente, Dipartimento di scienze neurologiche, Università degli Studi di Milano, Milano• Giulio Cossu, Stem Cell Research Institute, DIBIT, Fondazione Centro San Raffaele del Monte

Tabor, Milan

Sweden• Mallen Huang, 3H Biomedical AB, 3H Biomedical AB, Uppsala, SME

United Kingdom• Jennifer E Morgan, Department of Pediatrics, Division of Medicine, Imperial college London, The

Dubowitz Neuromucular Unit, Hammersmith Hospital, Imperial College of Science, Technologyand Medicine, London


MOLECULAR MECHANISMS OF NEURONAL DEGENERATION:FROM CELL BIOLOGY TO THE CLINIC

Proposal acronym NEURONE EC contribution (€) 8.300.000Contract n° LSHM-CT-2004-512039 Instrument NoEDuration (starting date) 4 Years (01.01.05) Participants 29

Abstract:

NeuroNE is Europe’s premiere research network for the creation of novel therapeutic approaches to neurodegenerativedisease and neurotrauma, which represent an urgent socio-economic and human need. The NeuroNE consortium (22academic groups, 5 SMEs and 1 management partner in 9 different countries) is taking a multi-disciplinary (functionalgenomics and proteomics, physiology, chemistry, clinical studies) and multi-faceted (disease mechanisms, biology of celldeath and survival, regeneration mechanisms, high-throughput screening, gene- and cell-based therapies) approach tothis problem. Among the neurodegenerative diseases, the network is focussing on Alzheimer's disease (AD), Parkinson'sdisease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). Spinal cord injury (SCI) will be themain model for neurotrauma. NeuroNE brings together investigators from different backgrounds (basic scientists, activeclinicians and therapeutically-oriented SMEs) to work at all levels on the target diseases using the methods of post-genomic science, molecular and cell biology, animal models, therapeutic strategies and clinical studies. Professionalproject management provides efficient integration, realization of scientific objectives and knowledge management. Thescientific infrastructure of the network includes shared NeuroNE-funded core facilities in 7 centres. The network hasemployed a team of scientists based in the participating laboratories who will conduct research and form collaborationsamongst the different participants. The network has a program of scientific meetings that will consist of three majorinternational plenary meetings and ten scientific workshops on specific topics. To feed back the benefits of integrationinto EU society, the network is working with patient organizations, identified associated research groups who will benefitimmediately from our infrastructures, and has opened network meetings to identified scientists from emerging researchcentres.

Web site: http://www.euneurone.net

Participants:

Coordinator

United Kingdom

Prof. James Fawcett, UNICAM, Cambridge University Centre for Brain Repair, Cambridgetel: +44 1223 33 11 88 fax: +44 1223 33 11 [email protected]

Belgium• Bart De Strooper, Flanders Interuniv. Inst. Biotechnology VZW, Depart. Human Genetics, Leuven

France• Nicole Deglon, URA CEA CNRS 2210 & ImaGene Program, Service Hosp. Frederic Joliot, Orsay• Brigitte Pettmann, Institut Nationale de la Sante et de la Recherche Medicale, UMR 623, Marseille• Jonathan Dando, Inserm Transfert Sa, European Project Management Department, Paris• Rebecca Pruss, Trophos SA, Marseille, SME• Jean-Chretien Norreel, Pharmaxon, R&D, Marseille, SME• Harold Cremer, Centre Nationale de la Recherche Scientifique, IBDM, Marseille

Germany• Hilmar Bading, Ruprecht-Karls-Universitaet Heidelberg, Institute of Neurobiology, Heidelberg• Mathias Baehr, UKG-GOE, Center for Neurological Medicine, Depart. Neurology, Goettingen• Christian Haass, Universitaet Muenchen, Adolf-Butenandt-Inst of Biochemistry, Munich• Rudiger Klein, Max-Planck-lnstitute of Neurobiology, Depart. Mol. Neurobiology, Martinsried• Bernhard Landwehrmeyer, Universitaetsklinikum Ulm, Department of Neurology, Ulm• Angelika Bonin-Debs, Xantos Biomedicine AG, R&D, Munchen, SME• Andreas Bosio, Memorec Biotec GmbH, Cologne, IND

Israel• Aaron Ciechanover, Technion - Israel Institute of Technology, Department of Biochemistry,

Faculty of Medicine, Haifa

Italy• Ernesto Carafoli, Istituto Veneto di Medicina Molecolare, Padova• Elena Cattaneo, Universita degli Studi di Milano, Dipartimento di Scienze Farmacologiche, Milano• Pier-giorgio Strata, Rita Levi Montalcini Center for Brain Repair, Dipart. di Neuroscienze, Turin

Spain• Jose Ramon Naranjo Orovio, Consejo Superior de Investigaciones Cientificas, Centro Nacional

de Biotecnologia, Depto. Molec. Cell. Biol. , Madrid• Cristina Garmendia, Genetrix S.L, Tres Cantos, Madrid, SME

Sweden• Patrik Brundin & Anders Bjorklund, Lunds Universitet, Wallenberg Neuroscience Center, Faculty

of Medecine, Lund• Carlos Ibanez, Karolinska Institutet, Depart. Neuroscience, Div. Mol. Neurobiology, Stockholm

Switzerland• Patrick Aebischer, Swiss Federal Inst. Technology, Inst. Neurosciences, Lausanne• Pico Caroni, Zweigniederlassung Friedrich Miescher Institute Biomedical Research (FMI), Basel• Ann Kato, University Geneva, Dept. Neuroscience, Faculty of Medicine, Geneva• Martin Schwab, University Zurich, Neurowissenschaften, Zurich

United Kingdom• Nigel Leigh, Kings College London, Depart. of Neurology, Institute of Psychiatry, London


THE DISCOVERY OF FUTURE NEURO-THERAPEUTIC MOLECULES

Proposal acronym NEUROscreen EC contribution (€) 2.050.000Contract n° LSHB-CT-2006-037766 Instrument STREPDuration (starting date) 3 years (01.01.06) Participants 9

Abstract:

NEUROscreen is an industry-lead project combining novel neural stem cell bioassays & post-genomic chemical geneticsto discover potential drugs of relevance to neurological diseases, regenerative medicine & cancer. Small moleculeinhibitors of the growth of clonal, human neural cancer stem cells have the prospect of being unique medicines targetingthe elusive cancer stem cell. Chemical modulators augmenting the growth, survival or differentiation of normal brain cellshave a prospect as preventative or regenerative medicines for neurodegenerative diseases i.e. Alzheimer's, stroke &Huntington¿s disease. The consortium will use quality controlled cell lines & genetic engineering technology to designunique bioassays with which the biological modulating capacity of small molecules will be evaluated in a multi-replicatemanner. Advanced chemistry will be used for the intuitive design and synthesize of biologically active molecules.Screening will be achieved with cells made to a quality & quantity via innovative bioprocesses & handled with state of theart robotics. The project will enhance the utility of the cell lines by delimiting the in vitro neural potency of the stem cells;ongoing determination of differentiation capacity serves as a rigorous confirmation of utility. The project will focus onspecific activities germane to a wider applied research field than its seeding project EuroStemCell. The consortium &project have been designed with a crucial alignment in mind to objectives of the Work Programme/Specific Programme forIntegrating & strengthening the ERA i.e. gender & innovation aspects in research, international cooperation (3 countries &a new member state) and fostering ethical awareness in research involving human stem cells. More than 50% of partnersrepresent European small- & medium-sized companies and this balance structures a consortium with greater potentialthan individual parts & will directly strengthen the ERA foundations.

Web site: not yet

Participants:

Coordinator

Germany

Dr. Timothy Allsopp, Stem Cell Sciences UK Ltd, Edinburgh, SMEtel: +44 131 650 5850 fax: +44 131 662 [email protected]

Germany• Stefanie Terstegge, Cellomics Platform, Robotics department, Life & Brain GmbH, Bonn, SME• Oliver Brüstle, Institute of Reconstructive Neurobiology, Rheinische Friedrich Wilhelms Universität

Bonn, Bonn

Italy• Dorotea, Rigamonti, Dialectica srl, Milan• Pasquale De Blasio, BioRep SrL, Milan• Luciano Conti, Department of Pharmacological Sciences and Center of Excellence on

Neurodegenerative Diseases, Università degli Studi di Milano, Milan

United Kingdom• Austin Smith, Institute for Stem Cell Biology, The Chancellor, Master and Scholars of the

University of Cambridge, Cambridge• François Guillemot, Division of Molecular Neurobiology, National Institute for Medical Research,

Medical Research Council, London


NERVOUS SYSTEM REPAIR

Proposal acronym NSR EC contribution (€) 2.600.335Contract n° MRTN-CT-2004-504636 Instrument Marie-Curie RTNDuration (starting date) 4 years (01.01.2004) Participants 8

Abstract:

Diseases and injuries that affect central nervous system neurons are among the illnesses that are hardest to cure. Theirfrequency increases dramatically with the ageing of the EU population. The complexity of these illnesses and the high-tech nature of planned therapeutics makes research in this field discouragingly expensive for the pharmaceutical industryand SME investors. European funding will allow us to bring into play almost the complete range of techniques that arecurrently applied to the nervous system.Clinicians, industrial partners and patient groups are also involved and will contribute both to the training and to theorientation of this joint Programme. Results generated by this network are likely to have significant effects on futuretherapies of patient affected by neurotrauma and neurodegenerative diseases.Our overall strategy is to use new scientific findings to further advance the technologies of brain repair to the point wherethey can be considered as viable clinical strategies. The main technological approaches can be applied across the rangeof damaging conditions of the central nervous system (CNS). They are: Stem cell/cell therapy, Protection/trophic factors,Gene therapy, regeneration/plasticity. Backing these up are enabling technologies: proteomics, genomics/post genomics,drug discovery, clinical protocols/preliminary trials, imaging, animal models.

Web site: http://www.euneuro.net/project

Participants:

Coordinator

France

Dr. Christopher Henderson, Developmental Biology Institute of Marseille (IBDM), Marseilletel: +33 491 26 97 60 fax: +33 491 26 97 [email protected]

Germany• Mathias Bähr, Göttingen University Neurological Clinic, Göttingen• Rüdiger Klein, Max Planck Institute of Neurobiology, Martinsried

Italy• Piergiorgio Strata, University of Turin, Department of Neuroscience, Turin

Switzerland• Patrick Aebischer, Swiss Federal Institute of Technology (EPFL), Lausanne

Sweden• Patrik Brundin, Wallenberg Neuroscience Center, Lund• Carlos Ibáñez, Karolinska Institute, Stockholm

United Kingdom• James Fawcett, Cambridge University Centre for Brain Repair, Cambridge


BONE FROM BLOOD:OPTIMISED ISOLATION, CHARACTERISATION AND OSTEOGENIC INDUCTION

OF MESENCHYMAL STEM CELLS FROM UMBILICAL CORD BLOOD

Proposal acronym OsteoCord EC contribution (€) 2.486.000Contract n° LSHB-CT-2006-018999 Instrument STREPDuration (starting date) 3 years (01.01.2006) Participants 9

Abstract:

There is an urgent clinical requirement for appropriate bone substitutes that are able to replace current autologous andallogeneic grafting procedures for the repair of diseased or damaged skeletal tissues. Mesenchymal stem cells (MSCs),found predominantly in the bone marrow, are able to differentiate into osteogenic, chondrogenic, adipogenic andtenogenic lineages, thus offering considerable therapeutic potential for tissue engineering applications. However, invasiveextraction procedures and insufficient viable cell yields have necessitated the identification of alternative tissue sources ofMSCs. Growing evidence suggests that umbilical cord blood (UCB) contains a population of rare MSCs that are able toundergo multilineage differentiation. The aim of this proposal is optimise the isolation and expansion of MSCs from humanUCB (CB-MSCs). The differentiation capacity of CB-MSCs will be examined, with a specific focus on osteogenesis. TheCB-MSCs will be characterised by genomic, proteomic and bioimpedance profiling, pre- and post-osteogenicdifferentiation, and compared to MSCs isolated from human bone marrow as well as embryonic stem cells. Fullbioinformatics integration of datasets will identify specific and/or novel signalling factors associated with CB-MSCs. Theimmunophenotype and alloreactivity of CB-MSCs will be determined. Comparative analyses of the population doublingtimes, telomere length and telomerase activity will identify the lifespan of CB-MSCs. Novel expansion techniques will becombined with scale-up procedures and the generation of CB-MSC lines for banking using optimised cryopreservationprotocols. In vitro and in vivo biocompatibility assays using a range of biomimetic scaffolds will be exploited,complementing in vivo homing and engraftment models. Our integrated approach using complementary expertise willprovide a timely and thorough evaluation of CB-MSCs and define appropriate routes for their therapeutic implementation.

Web site: http://www.bonefromblood.org

Participants:

Coordinator

United Kingdom

Dr. Paul Genever, Biology, University of Yorktel: +44 1904-328649 fax: +44 [email protected]

Denmark• Moustapha Kassem, Department of Endocrinology, University Hospital of Odense, Odense• Jens Andersen, Center for Experimental Bioinformatics, Department of Biochemistry and

Molecular Biology, University of Southern Denmark, Odense

Germany• Hagen Thielecke, Biohybrid Systems Department, Fraunhofer Institute for Biomedical

Engineering, St. Ingbert, München• Hermann Eichler, Institute of Transfusion Medicine & Immunology, Stem Cell Laboratory, Faculty

of Clinical Medicine Mannheim, University of Heidelberg, Mannheim

Israel• Yaron Daniely, Gamida-Cell, Ltd. Cell Therapy Technologies, Jerusalem, SME

Portugal• Helder Cruz, ECBio Investigação e Desenvolvimento em Biotecnologia S.A., Oeiras, SME

United Kingdom• Lee D.K. Buttery, Tissue Engineering Group, School of Pharmacy, University of Nottingham• Robin Andrew Quirk, Regentec Ltd, Nottingham, SME


GENE THERAPY FOR EPIDERMOLYSIS BULLOSA:A MODEL SYSTEM FOR TREATMENT OF INHERITED SKIN DISEASES

Proposal acronym SKINTHERAPY EC contribution (€) 2.079.900Contract n° LSHB-CT-2005-512073 Instrument STREPDuration (starting date) 3 years (15.04.05) Participants 8

Abstract:

The project aims to develop a gene therapy technology model based on autologous transplantation of skin made in vitrofrom genetically modified epidermal stem cells. This includes developing vectors, gene transfer technology, and preclinicalmodels of gene therapy of rare inherited defects treatable with sustained local delivery of a recombinant protein. Theresearch focuses on dystrophic epidermolysis bullosa (DEB), a rare, disabling skin disease caused by inherited defects ofcollagen type VII. The workplan consists in: - Recruiting, genotyping and characterizing at molecular level cohorts ofpatients with recessive and dominant DEB - Isolating epithelial stem cells from the skin of DEB patients and DEB dogs, aspontaneous large animal model for the disease - Developing viral vectors (oncoretroviral, lentiviral, and hybridadeno/AAV vectors) to integrate and stably express the collagen VII cDNA in DEB epidermal stem cells ex vivo -Transducing highly clonogenic DEB keratinocytes with the most appropriate vector(s) - constructing skin equivalentsmade with genetically corrected DEB cells to assess the full morphological and functional reversion of the DEB phenotype- Constructing transplantable epithelia using genetically corrected DEB cells and preclinical assessment of theirperformance in vivo in appropriate immune competent animal models - Developing a technology for production anddownstream processing of clinical-grade viral vectors preparations under GMP/GLP standards - Establishing SOP,protocols and guidelines to genetically modify epidermal stem cells used to produce skin implants for clinical use -Disseminating results. The project�s immediate goal is to develop a gene therapy approach to DEB and designappropriate phase I/II clinical trials to exploit the knowledge generated. This research ultimately targets theimplementation of a technology applicable to other genetic protein deficiencies requiring local or systemic delivery ofactive molecules.

Web site: http://www.debra-international.org/researche1.htm

Participants:

Coordinator

France

Prof. Guerrino Meneguzzi, Institut National de la Santé et de la Recherche Médicale, Nicetel: +33 4 93 37 77 79 fax: +33 4 93 81 14 [email protected]

France• Jonathan Dando, INSERM Transfert SA, Paris

Germany• Leena Bruckner-Tuderman, Universitaetsklinik Freiburg

Italy• Michele De Luca, Fondazione Banca Degli Occhi del Veneto O.N.L.U.S., Venezia-Mestre• Fluvio Mavilio, Universita' di Modena e Reggio Emilia, Modena• Anna Stornaiuolo, Molecular Medicine S.p.A, Milan, SME

Spain• Jose Luis Jorcano Noval, Centro de Investigaciones Energeticas Medioambientales y

Tecnologicas, Madrid

United Kingdom• John Richard William Dart, DEBRA Europe, Crowthorne


EMBRYONIC STEM CELLS FOR THERAPY AND EXPLORATION OFMECHANISMS IN HUNTINGTON DISEASE

Proposal acronym STEM-HD EC contribution (€) 2500.000Contract n° LSHB-CT-2006-037349 Instrument STREPDuration (starting date) 3 years (01.12.06) Participants 8

Abstract:

Embryonic stem cell (ES) lines have potential interest for exploring mechanisms and therapeutics of genetically-determined diseases, due to their fundamental attributes, unlimited expansion and pluripotency: isogenic cells of anyphenotype can be produced in any requested amount. STEM-HD aims at validating this potential for Huntington's disease(HD), on the basis of the analysis of ES cell lines expressing the mutant HD gene. These will be obtained either followingderivation after pre-implantation genetic diagnosis from an embryo expressing the mutant huntingtin gene (existing cellline) or through engineering of existing native human and mouse ES cell lines. The consortium will:- establish protocols to enrich ES cell progeny in cell phenotypes of interest, in particular striatal GABA neurons.- design and implement infrastructures for mass cell production and long-term cultures of ES cells either undifferentiatedor following guided differentiation.- identify, using large-scale "resource-driven" approaches, HD biomarkers in mutant HD-expressing ES cells progenyappearing as alteration in the expression of genes (transcriptome). Mutant-association of these molecular markers will bevalidated using patients¿ samples and assays developed.- explore the mechanisms of the diseases in the mutant HD-expressing ES cells progeny using functional genomics (RNAiand gene overexpression) and "hypothesis-driven" approaches.- perform high content drug screening on HD gene-carrying ES cell progeny using validated biomarkers as signals andavailable compounds libraries.

Web site: not yet

Participants:

Coordinator

France

Dr. Marc Peschanski, Unité 421-ISTEM, Institut National de la Santé et de la RechercheMédicale, Evrytel: +33 169471150 fax: +33 [email protected]

Belgium• Karen Dora Sermon, Research Group Reproduction and Genetics, Vrije Universiteit Brussel,

Brussels

France• Jacques Haiech, Institut Gilbert Laustriat UMR CNRS 7175, University Strasbourg / Louis

Pasteur, Illkirch• Abderrahim Mahfoudi, European Projects Management Department, Inserm Transfert, Paris

Israel• Joseph Itskovitz-Eldor, Department of Obstetrics and Gynecology, Rambam Medical Center,

Technion - Israel Institute of Technology, Haifa

Italy• Dorotea Rigamonti, Dialectica srl, Milano, SME• Elena Cattaneo, Department of Pharmacological Sciences and Center of Excellence on

Neurodegenerative Diseases, Università degli Studi di Milano, Milan

United Kingdom• Nicholas Allen, School of Biosciences, Cardiff University, Cardiff


PRE-CLINICAL EVALUATION OF STEM CELL THERAPY IN STROKE

Proposal acronym STEMS EC contribution (€) 2.400.000Contract n° LSHB-CT-2006-037328 Instrument STREPDuration (starting date) 3 years (01.12.06) Participants 9

Abstract:

Using stem cells (SC) multipotent properties has become a challenging research field for most clinical areas, especially indisciplines lacking treatment options such as brain disorders and lesions. In particular, stroke or ischemic cerebrovasculardisease accounts for roughly half of the patients hospitalised for neurological diseases and is associated with a largeproportion of the health care costs in Europe. Until now, all neuroprotective approaches having yielded positive results inanimal models have proven ineffective in clinical trials.SC clonal populations expected capacity to self-renew and differentiate efficiently into the desired cell type promise toproduce beneficial effects in many diseases. Several studies indicate the therapeutic potential of SC in stroke aftertransplantation of various SC types.However, standardisation of conditions to regulate SC proliferation and differentiation to produce the «ideal» graft need tobe better defined; changes induced by their transplantation into lesioned brain structures are unknown, as is the full extentof functional improvement at long-term post-stroke delays. STEMS deals with the therapeutic aim of using SC to reducestroke-induced brain dysfunctions. Its main objective is to determine the extent and limits of SC therapy in stroke to pavethe way for clinical trials. It will be achieved through the completion of six successive and complementary goals:- Definition of standard experimental conditions for proliferation, guided differentiation and mass-production- Identification of the best transplantation protocol regarding post-stroke delays in a rat model of focal ischemia- Control of safety and compatibility aspects- Quantification of the effects of SC transplantation on functional impairments- Transposition of the optimal experimental conditions to non-human primates- Definition of the relevant human cell therapy product and operating procedures to be applied to stroke patient

Web site: not yet

Participants:

Coordinator

France

Dr. Brigitte Onteniente, INSERM UMR 421, Institut National de la Recherche Médicale, Créteiltel: +33 01 49 81 36 72 fax: +33 01 4981 [email protected]

Denmark• Vagn Holmegaard, Medical Biotechnology Center, The University of Southern Denmark, Odense

France• Philippe Hantraye, URA CEA CNRS 2210, Service Hospitalier Frédéric Joliot, Commissariat à

l'Energie Atomique, Orsay• Karine Baudin, European Project Management Department, INSERM-Transfert, Paris

Germany• Klaus G. Reymann, Projet Group Neuropharmacology, Leibniz Institute for Neurobiology,

Magdeburg

Sweden• Patrik Brundin, Department of Experimental Medical Science/Medical Faculty/Division of

Neuroscience/Neuronal Survival Unit, Lunds Universitet, Lund• Jonas Frisén, Department of Developmental Biology/Cell and Molecular Biology Program/Frisén

Group, Karolinska Institutet, Stockholm• Johan Hyllner, Cellartis AB, Göteborg, SME


REDUCING ANIMAL EXPERIMENTATIONIN PRECLINICAL PREDICTIVE DRUG TESTING BY HUMAN

HEPATIC IN VITRO MODELS DERIVED FROM EMBRYONIC STEM CELLS

Proposal acronym SyntheGeneDelivery EC contribution (€) 2.400.000Contract n° LSHB-CT-2005-018716 Instrument STREPDuration (starting date) 3 years (01.12.05) Participants 6

Abstract:

Our aim is to develop SyntheGeneTransfer (SGT), a new ex-vivo gene delivery protocol to provide stable long-termexpression of integrated transgenes. Our clinical objective is to provide gene therapy solutions for some genetic diseasesof the neuromuscular and skeletal systems as well as circulating-polypeptide deficiencies that together afflict over35,000,000 patients in Europe. We have therefore selected mesenchymal and muscle stem cells as model systems inwhich to develop the SGT protocol.The SGT protocol is designed to overcome three key barriers: transgeneinternalization in stem cells, transport across the nuclear membrane and integration at a predefined ?safe? genomic locusthat will permit transgene expression. To achieve these goals and fully develop the technology, this application drawstogether a multi-disciplinary European team from four public laboratories and two SMEs. To overcome serious problemswith current transfection methods, the teams will develop protocols for internalization and nuclear membrane transportbased on Lipoplex, block copolymers and Bioplex. To overcome serious problems with current integration systems, a newtargeted transposition system will be developed using a Mos1 mariner transposon.Our main technical objective is toengineer SGT to provide a method for the integration of large transgenes that will be both highly efficient and maintain astringent level of safety by preventing the oncogenic transformation of the target cells. Optimization of the cellularinternalization and nuclear import steps will allow the cells to be treated with a minimal amount of the transgene. This willminimize the probability of illegitimate integration events at unexpected genomic loci. To optimize the integration step ofthe process, the Mos1 transposon will be engineered to allow targeting to specific loci. The system will also be engineeredto accept large transgenes without the concomitant loss of efficiency observed with existing systems.

Web site: not yet

Participants:

Coordinator

France

Dr. Yves Bigot, Etude des Parasites Génétiques - EA3868, Université François Rabelais, Tourstel: +33 247367035 fax: +33 [email protected] [email protected]

France• Bruno Pitard, In Cell Art, Nantes, SME

Sweden• Elisabeth Törnquist, Avaris AB, Solna, SME• C.I. Edvard Smith, Clinical Research Center, Karolinska Institutet, Stockholm

United Kingdom• Ronald Chalmers, Department of Biochemistry, University of Oxford• Dominic Wells, Laboratory: Gene Targeting Unit, Division of Neuroscience, Technology and

Medicine, Faculty of Medecine, Imperial College of Science, Technology and Medicine, London


DEVELOPMENT AND PRECLINICAL TESTING OFCORD BLOOD-DERIVED CELL THERAPY PRODUCTS

Proposal acronym TherCord EC contribution (€) 1.800.000Contract n° LSHB-CT-2006-018817 Instrument STREPDuration (starting date) 3 years (01.05.2006) Participants 9

Abstract:

Cord blood is a widely recognized source of hematopoietic progenitor cells for human transplantation in pediatric and, to alesser extent, also adult patients affected by different hematological disorders. The therapeutic perspectives of cord bloodhas been recently widened by the discovery that it contains pluripotent stem cells, capable to give rise, in vitro and in vivo,to other than hematopoietic cells. The present project is aimed at investigating the potential of cord blood stem cells fordifferentiation and tissue repair, with the final goal to develop novel technologies for pre-clinical testing of cord blood-derived cell therapy products. Therefore, the main part of this project will be dedicated to set up and validate innovativetechnologies for the isolation, amplification and differentiation of pluripotent cells from cord blood, including immunologicalassays for the evaluation of their immunoreactivity and animal models of human diseases to test their safety and efficacy.Moreover, the presence of a SME in the Consortium is specifically aimed at translate the results obtained from the basicscience into GMP procedures to be used in phase I/II clinical protocols.

Web site: under construction

Participants:

Coordinator

Italy

Dr Lorenza Lazzari, Centro Trasfusionale e di Immunologia dei Trapianti, Ospedale MaggiorePoliclinico di Milano IRCCS, Milantel: +39 255034053 fax: +39 [email protected]

Germany• Anna Magdalene Wobus, Cytogenetics Department, Research Group: In Vitro Differentiation,

Institut für Pflanzengenetik und Kulturpflanzenforschung, Gatersleben

Israel• Yaron Daniely, Alliance Manager & Research Team Leader, Gamida-Cell Ltd. Cell Therapy

Technologies, Jerusalem, SME

Italy• Maurizio Pesce, Laboratorio di Biologia Vascolare e Terapia Genica, Centro Cardiologico

Monzino, Milan• Rita Maccario, Divisione di Oncoematologia Pediatrica, Laboratorio di Ricerca Area Trapianti,

Immunologia dei Trapianti, IRCCS Policlinico San Matteo di Pavia, Pavia

Netherlands• Willem E. Fibbe, Department of Hematology, Leiden University Medical Center, Leiden

Spain• Joan Garcia, Barcelona CBB, Barcelona Cord Blood Bank (BCB) Centre de Transfusio I Banc De

Teixits - Serveis de Referencia de Catalunya, Barcelona

United Kingdom• Dominique Bonnet, Haematopoeitic Stem Cell Laboratory, London Research Institute, Cancer

Research UK, London• Marcela Contreras, National Directorate of Diagnostics, Development & Research - National

Blood Service, London


MODULATION OF THE RECRUITMENT OF VESSELS AND IMMUNE CELLSBY MALIGNANT TUMORS: TARGETING OF TUMOR VESSELSAND TRIGGERING OF ANTI-TUMOR DEFENSE MECHANISMS

Proposal acronym TUMOR-HOST GENOMICS EC contribution (€) 2.700.000Contract n° LSHC-CT-2005-518198 Instrument STREPDuration (starting date) 3 Years (01.11.05) Participants 3

Abstract:

In addition to oncogenic mutations that act cell-autonomously, tumor cell growth depends on interactions with itsmicroenvironment. Tumor microenvironment consists of cells of hematopoietic and mesenchymal origin, includinginflammatory cells, stem and progenitor cells, fibroblasts, endothelial cells and vascular mural cells. Tumor cell growth isknown to depend on the interaction of tumor cells with such stromal cells. For example, growing tumor needs to recruitnormal endothelial and vascular mural cells to form its blood vessels. In addition, tumor cells induce stromal cells tosecrete factors that contribute to tumor cell growth and invasion. Stromal cell -dependent interactions represent anattractive target for cancer therapy, because normal cells are genetically stable, and would not be expected to developresistance to therapeutic agents. The development of such therapies is hampered by the fact that the molecularmechanisms behind tumor-stroma interactions are often poorly understood.In summary, the workplan entails development of novel advanced functional genomics instruments, technologies andmethods for methods to study tumor-host interactions in cancer, and to apply these techniques to the identification ofmolecules and processes in normal cells which could be targeted by novel anti-cancer therapeutic agents. In addition, wewill develop targeted lentiviruses which would allow in vivo delivery of therapeutic agents into tumors. Functionalvalidation of the discovered targets and developed delivery systems will be performed in vivo models of murine tumorgrowth and dissemination. The work has significant exploitation potential, and applications for health in theunderstanding of the molecular mechanisms of tumor-host interactions, and in the treatment of cancer.

Web site: none

Participants:

Coordinator

Finland

Dr. Petri Salven, Faculty of Medicine, Developmental and Reproductive Biology ResearchProgram, Helsingin yliopisto, University of Helsinki, Helsinkitel: +35 8919125384 fax: +35 [email protected]

Italy• Luigi Naldini, Angiogenesis and Tumor Targeting Research Unit, Fondazione Centro San Raffaele

del Monte Tabor, Milan

Netherlands• Peter ten Dijke, Division of Cellular Biochemistry, Antoni van Leewenhoek Hospital, The

Netherlands Cancer Institute, Leiden


X-LINKED ADRENOLEUKODYSTROPHY (X-ALD):PATHOGENESIS, ANIMAL MODELS AND THERAPY

Proposal acronym X-ALD EC contribution (€) 1.800.000Contract n° LSHM-CT-2004-502987 Instrument STREPDuration (starting date) 3 years (01.01.04) Participants 6

Abstract:

Our ultimate goal is to develop new therapies for X-linked adrenoleukodystrophy (X-ALD), the most frequent inheritedmonogenic demyelinating disease of the central nervous system (1:18,000). X-ALD is characterised by extensivephenotypic variability, which is not correlated to ALD genotype, and leads to death in boys due to cerebral demyelinationand to motor disability in adults due to spinal cord degeneration. Allogenic bone marrow transplantation, proven to bebeneficial in X-ALD, can be applied only to a limited number of X-ALD patients. Thus, there is no treatment for the majorityof patients, in particular those with the severe cerebral form of X-ALD and adults with adrenomyeloneuropathy (AMN).Understanding of the pathogenesis is necessary for the development of novel therapeutic strategies. The still unresolvedtransporter function of the ALD protein will be studied in reconstituted liposomes. To get further insight into thepathogenesis of X-ALD, we aim to identify genes and proteins that are differentially regulated in the target tissues ofpatients with cerebral ALD and AMN using Affymetrix analysis of differential mRNA expression and a proteomicsapproach based on MALDI-TOF mass spectrometry. Additional genome-wide approaches such as mapping ofquantitative trait loci will be applied to identify modifier genes that may contribute to the phenotypic variability of X-ALD.We will generate new mouse models that represent a wider phenotypic spectrum of the disease for a more efficientevaluation of therapeutic strategies. Furthermore, we will evaluate four promising new therapy strategies: ALD genetransfer into haematopoietic stem cells, into mesenchymal stem cells, and by direct injection of viral vectors, andpharmacological induction of a related gene as a substitute for the deficient ALD gene. Only the joint effort of the highlyqualified partners of this proposal will allow achieving our ambitious aims.

Web site: none

Participants:

Coordinator

Austria

Prof. Dr. Johannes Berger, Brain Research Institute, University of Viennatel: +43 1 42 77 62 812 fax: +43 1 4277 [email protected]

France• Patrick Aubourg, Institut national de la santé et de la recherche médicale, Paris• Jean-Michel Mandel, Human Molecular Genetics Group, IGBMC, Strasbourg

Germany• Peter Geigle, CellMed AG, Alzenau, SME• Klaus-Armin Nava, Max-Plank-Institute of Experimental Medicine, Göttingen

Netherlands• Ronald Wanders, Academic Medical Center, Dept. Clinical Chemistry, Paedriatrics & Neurology,

University of Amsterdam


BUILDING

Tissue engineering

47

THIRD GENERATION SCAFFOLDSFOR TISSUE ENGINEERING & REGENERATIVE MEDICINE

Proposal acronym 3G-SCAFF EC contribution (€) 1.699.998Contract n° NMP3-CT-2005-013602 Instrument STREPDuration (starting date) 3 years (01.03.05) Participants 7

Abstract:

We propose to use cells as micro-factories to produce and assemble the molecular components at the nanometer levelwhich is not possible by conventional mechanical engineering. This cellular engineering will be used to produce thesupportive structure with desired shape, compliance and mechanical strength at meso- and macroscale levels. Weachieve this by engineering cells to express the desired components creating bioartificial scaffolds which mimick thenatural extracellular matrix and will fulfil the requirements of mechanical support, compartmentalization, storage andsequestration of molecules. This also will have correct porosity allowing for diffusion of soluble molecules and access tocells, exposing ligands for adhesion and proliferation and being degradable by enzymatic mechanisms to allow bodydirected remodelling.

Web site: http://www.3gscaff.uu.se

Participants:

Coordinator

Sweden

Prof. Jöns Hilborn, Uppsala University, Polymer Chemistry, Uppsalatel: +46 18 471 3839 fax: +46 18 471 [email protected]

Germany• Thomas Gries, Aachen University of Technology, Institut für Textiltechnik (ITA), Aachen

Sweden• Mikael Sellman, Karocell Tissue Engineering AB, Stockholm IND

Switzerland• Florian Wurm, Swiss Federal Institute of Technology, Lab. Cellular Biotechnology, Lausanne• Peter Frey, Lausanne Research Hospital, Dept. of Pediatric Urology, Laboratory for Experimental

Pediatric Urology, Lausanne

United Kingdom• Robert Brown, University College London, Inst. Orthopeadics Musculo-Skeletal Science, London• John Michael Garland, Tissue Works Ltd / University of Manchester IND

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G3 Materials

PRODUCTION UNIT FOR THE DECENTRALISED ENGINEERING OFAUTOLOGOUS CELL-BASED OSTEOINDUCTIVE BONE SUBSTITUTES

Proposal acronym AUTOBONE EC contribution (€) 2.296.892Contract n° NMP3-CT-2003-505711 Instrument STREPDuration (starting date) 4 years (01.01.04) Participants 12

Abstract:

Bone is among the most frequently transplanted tissues and autografìe account for the majority of bone graft procedures.However, autografts always require a secondary surgery adding high costs to health services, increase patient morbidityand are available in very limited quantities. Therefore, there is widespread interest around the world for programmes torebuild and restore function of degenerative tissue using artificial implant materials. The enormous need for bone graftsand the recent progresses in biomedical and biomaterial sciences have stimulated the rapid growth and expansion of anew field: bone tissue engineering. However, this approach presents important limits to the transfer from an academic toa routine clinical environment: high cost, difficulties in transferring biological samples between hospitals and centralized"cell factories"; reproducibility due to lack of standards. The aim of this project is to combine the developments in theareas of tissue engineering based on materials and 3D scaffolds development with largely laboratory and fewcommercial activities in the field of bioreactors and transpose the concepts of tissue engineering and regeneration of thefrontiers of new developments: the automated production of autologous bone replacement materials.The goal of this project is to develop a bioreactor that would be set-up within the confínes of a hospital and which wouldbe used to homogenously activate specially designed porous matrices with stem cells from harvested bone marrowaspirates of the patient to produce autologous hybrid bone graft materials. The result would be an innovative technologyto produce bone substitute materials having biological properties approaching those of autologous bone, the goldenstandard of the bone substitute, and would be completely biocompatible.This target will be achieved through the following scientific and technical objectives: 1) design and production ofinnovative bioreactors, 2) design and production of novel biomaterials and scaffolds architectures tailored for bothbioreactor use and bone tissue engineering, 3) validation of the approach in preclinical animal studies.

Web site: http://istec.cnr.it/autobone

Participants:

Coordinator

Italy

Dr. Anna Tampieri, Inst. Science & Technology for Ceramics - National Research Council, Faenzatel: +39 05 46 699 740 fax: +39 05 46 463 [email protected]

Denmark• Naseem Theilgaard, Danish Technological Institute, Taastrup• Søren Overgaard, Department of Orthopedics, Odense University Hospita, Odense

France• Marie-Françoise Harmand, Laboratoire d'Evaluation des Matériels Implantables, Martillac• Christian Rey, Institut National Polytechnique de Toulouse

Germany• Achim Stangelmayer, Presens Precision Sensing Gmbh, Regensburg, SME• Charles James Kirkpatrick, Johannes Gutenberg University of Mainz

Italy• Martinetti Roberta, Fin-ceramica faenza, Faenza (Ravenna), SME• Rodolfo Quatro, Dipartimento di Oncologia, Biologia e Genetica - Università di Genova

Spain• Elena Fuentes Carazo, Fundacion Tekniker, Eibar

Switzerland• Ivan Martin, University of Basel• Dr Roberto Tommasini, Millenium Biologix AG, Schlieren-Zürich, SME


DEVELOPMENT OF A BIOARTIFICIAL PANCREAS FOR TYPE I DIABETES THERAPY- NANOTECHNOLOGY BIOMATERIAL ENGINEERING TRANSPLANTATION

Proposal acronym BARP+ EC contribution (€) 2.495.600Contract n° NMP3-CT-2003-505614 Instrument STREPDuration (starting date) 3 years (01.01.04) Participants 14

Abstract:

Four to five million people in Europe and about 80 million worldwide suffer from type 1 diabetes (insulindependent),characterized by a deficiency in insulin secretion resulting in hyperglycaemia responsible for debilitating long-termcomplications (coronary diseases, acquired blindness, chronic renal failures). Recently developed immunosuppressiveprotocols improved the success of human allogenic pancreatic islets transplantation. However, such transplantation hassevere limitations: the number of available donors and the potential toxicity of the immunosuppressive treatments. Toavoid immunosupression, islets could be encapsulated to protect them from the attack of the immune system and thusfrom rejection. This project intends to develop, improve and validate an efficient reliable bioartificial pancreas for humanapplication. To achieve this ambitious goal, various disciplines are integrated in a true task force of basic and clinicalresearchers with leading expertise in experimental diabetes and advanced modern material technologies to develop aneffective approach for the treatment of type 1 diabetes. The proposed approach takes into account the far-reachingadvances in the modern nanosize technology, which are of utmost importance for the success of this challenge. To carryout the project to a successful achievement, the consortium gathers a multidisciplinary group of leading Europeanscientists with complementary competencies, spanding from biomaterials to tissue engineering, and high-tech SMEs.This transnational approach provides convincing solutions to bypass the limitations of traditional treatments of thisdisease. Such a device will improve the security of adequate insulin administration avoiding both unwanted hypoglycemicand hyperglycemic episodes and thereby improve the quality of life of patients.

Web site: https://mail.mapr.ucl.ac.be/wws/info/barp

Participants:

Coordinator

France

Dr. Alain Belcourt, Centre Européen d'études du Diabète, Strasbourgtel: +33 3 90 20 12 13 fax: +33 3 90 20 12 [email protected]

Belgium• Willi-Jean Malaisse, Université Libre de Bruxelles• Patrick Bertrand, Université Catholique de Louvain

France• Serge Piranda, Statice Santé, Besançon, SME• Gilbert Legeay, Association pour les Transferts de Technologies du Mans• Marie-Pierre Krafft, CNRS - Institut Charles Sadron, Strasbourg• Michel Bonneau, Institut National de la Recherche Agronomique, Jouy en Josas

Germany• Jorg Kandzia, Cell Concepts, Umkrich, SME• Karin Ulrichs, Julius Maximilians University Würzburg• Sigurd Lenzen, Medizinsche Hochschule Hanover

Italy• Piero Marchetti, Universita Di Pisa• Andrea Remuzzi, Instituto Di Ricerche Farmacologiche "Mario Negri", Bergamo• Allessandra Gliozzi, Biophysics Laboratory, University of Genova

Portugal• Pedro E. Cruz, Empresa de Consultoria em Biotechnologia, Oeiras, SME


INTELLIGENT BIOMATERIAL SYSTEMS FOR CARDIOVASCULAR TISSUE REPAIR

Proposal acronym BIOSYS EC contribution (€) 1.999.700Contract n° NMP3-CT-2005-013633 Instrument STREPDuration (starting date) 3 years (01.01.05) Participants 6

Abstract:

Cardiovascular diseases are the most frequent cause of mortality in Europe. Concomitant the main age of the Europeanpopulation will increase significantly in the next decades. To prevent the collapse of the health care system as a result ofthe unpayable clinic cost, new strategies have to be found. Tissue engineering is such a promising strategy tocompensate the disadvantages of conventional cardiovascular prostheses. A tissue replacement, engineered from apatient’s own cells, which can grow and replace the defective tissue, is here the superlative answer. Therefore theobjective of the BioSys project is to develop new intelligent biomaterial systems.Starting from common polymers, a biocompatible fibre with controllable degradation will be developed. The fibre will betested regarding degradation and biocompatibility. Required surface modifications will be carried out, focusing on theimprovement of biocompatibility. Different types of 3D-textile scaffolds will be designed and produced. As example forevaluation and implementation of the new intelligent biomaterial, cardiovascular implants will be evaluated and tissueengineered.The developed biomaterial will be the first material with controllable biodegradability and improved biocompability. Amaterial with these properties is not yet available in Europe or in other countries. European researchers will be the first todevelop and use this kind of intelligent biomaterial. BioSys demonstrates the competitiveness of European life scienceresearch. The results of the project could be transferred to other medical fields for a long term innovation. Theenhancement of knowledge in the field of tissue engineering and the development of new biomaterial will be a hugecontribution to increase the living quality of the population of the whole European Community, will reduce theconsequential costs in the health care system and guarantee an excellent place in further market of tissue engineeredproducts.

Web site: http://www.biosys-project.com

Participants:

Coordinator

Germany

Dr. Michael Klöppels, 3T TextilTechnologie-Transfer GmbH, Aachen INDtel: +49 241 96 33 750 fax: +49 241 96 33 [email protected]

Finland• Minna Kellomaki, Pertti Nousiainen & Ville Ella, Tampere University of Technology, Institute of

Fibre Materials Science, Tampere

Germany• Thomas Gries, Marvi Sri Harwoko & Ute Wiesemann, Rheinich-Westfälische Technische

Hochschule Aachen, Institut für Textiltechnik, Aachen• Stefan Jockenhövel & Jörg Sachweh, University Hospital Aachen, Clinic for thoracic and

cardiovascular surgery, Aachen

Ireland• Terry Smith, Abhay Pandit, William Carroll, Yuri Rochev & Valerie Barron, National University of

Ireland, National Centre for Biomedical Engineering Science, Galway

Switzerland• Simon-Philipp Hoerstrup, University of Zurich, Department of Tissue Engineering and Cell

Transplantation (Regenerative Medicine), Zurich


CELL PROGRAMMING BY NANOSCALED DEVICES

Proposal acronym CellPROM EC contribution (€) 17.599.928Contract n° NMP4-CT-2004-500039 Instrument IPDuration (starting date) 4 years (01.03.04) Participants 27

Abstract:

The vision of the IP is - in analogy to analytical High-Throughput Screening systems - to develop an automated devicefor the imprinting of cells via nanoscaled macromolecular landscapes, the NanoScapes. This will allow, for the first time,to non-invasively produce well-defined populations of individually programmed cells, eventually leading to substantialbreakthroughs and numerous applications in the fields of molecular medicine and cellular nano-biotechnology. We willbuild the NanoLandscaper, a demonstrator for this new generation of nano-biotechnological equipment, the CellPROMs.As the EPROM paved the way to a broad application of microelectronics, CellPROMs will overcome current limits of andrevolutionise the existing handling technologies and procedures by automated, compact and parallel yet still individualhandling of large numbers of cellular samples. Typical targets will be animal and human adult stem cells. The main taskof our IP is to develop procedures and devices for the precise creation of NanoScapes. Although surface imprinting ofcells will be realised via artificial nano-biotechnological devices, e.g. nanostructured stamps or beads, these tools aredesigned according to the natural principles of cellular signalling and differentiation. As nanocomponents are essential tothe imprinting process, suitable techniques and principles to form nanoscaled macromolecular patterns on arbitrarysurface geometries have to be developed. All components, ranging from the nanoscale of functional interfaces up to themacro level for cell handling, are needed as functional modules, ready for implementation into the demonstrator. Theproject features multiple nano- and biotechnological challenges. To tackle these, will lead to breakthroughs innanotechnological device development and, moreover, drastically advance our understanding of biological signalsrelevant to cellular programming. Once available, CellPROMs will facilitate the transition to a more knowledge-based andless resource-intensive society in Europe.

Web site: http://www.cellprom.net

Participants:

Coordinator

Germany

Prof. Guenter Fuhr, Fraunhofer-Institut für Biomedizinische Technik (IBMT), St. Ingberttel: +49 6894 980 0 fax: +49 6894 980 [email protected]

Austria• Franz Gabor, Univ. Vienna, Inst. Pharmaceutical Technology and Biopharmaceutics, Vienna

Belgium• Florence Xhonneurx, Eurogentec, Seraing, IND

France• Claude Leclerc, Institut Pasteur, Biologie des Regulations Immunitaires, Paris

Germany• Uwe Hartmann & Klaus Steingröver, Saarlandes Univ. & Inst. für Neue Materialien, Saarbrücken• Christiane Ziegler, Technische Universität Kaiserslautern, Kaiserslautern• Matin Daffertshofer, Evotec Technologies, Hamburg, IND• Jörg Scherer, European Research and Project Office, Saarbrücken• Hagen von Briesen, Georg-Speyer-Haus, Institute for Biomedical Research, Frankfurt am Main• Petra Zalud, tp21, Life Science, Saarbrücken, SME• Frank Saurenbach, Surface Imaging Systems (S.I.S.), Herzogenrath, SME• Michael Stuke, Max-Planck-Gesellschaft zur Förderung der Wissenschaften,Göttingen• Steffen Howitz, Gesellschaft für Silizium-Mikrosysteme (GeSiM), Grosserkmannsdorf, SME• Christian Moormann, AMO, AMICA (Advanced Microelectronic Center Aachen), Aachen, SME• Andreas Manz, Institut für Spektrochemie und Angewandte Spektroskopie, Dortmund

Israel• Ron Maron, Tel Aviv Univ. Research Institute for Nanoscience and Nanotechnology, Tel-Aviv

Italy• Giampaolo Minetti, University of Pavia, Dipartimento di Biochimica Sezione di Scienze, Pavia

Lithuania• Aivaras Kareiva, Vilnius Univ., Fac. Chemistry, Depart. General and Inorganic Chemistry, Vilnius

Portugal• Manuel Carrondo, instituto de Biologia Experimental e Tecnologica, Oeiras

Slovenia• Sasa Svetina, University of Ljubljana, Faculty of Medicine, Institute of Biophysics, Ljubljana

Spain• Josep Samitier, Univ. Barcelona, Bioelectronic & Nanobioscience res. center (CBEN), Barcelona

Sweden• Hans Hertz, Kungl Tekniska Högskolan, KTH Physics, Stockholm• Melene Andersson, Silex Microsystems AB, Jarfalla, SME

Switzerland• Philippe Renaud, Ecole Polytechnique Fédérale de Lausanne, Lausanne• Denis Bubendorf, Sysmelec, Gals, SME• Karl Brander, Leister Process Technologies, Microsystems Division, Kägiswil, IND

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G4 Nanosciences andnanotechnologies

THREE-DIMENSIONAL RECONSTRUCTION OF HUMAN CORNEASBY TISSUE ENGINEERING

Proposal acronym CORNEA ENGINEERING EC contribution (€) 2.558.797Contract n° NMP2-CT-2003-504017 Instrument STREPDuration (starting date) 3 years (01.04.04) Participants 15

Abstract:

The goal of the proposed research project is to reconstruct a human cornea in vitro, for use both in corneal grafting andas an alternative to animal models for cosmeto-pharmacotoxicity testing. The project responds to the urgent need todevelop new forms of corneal replacements as alternatives to the use of donor corneas, in view of of the world-wideshortage of donors, the increasing risk of transmissable diseases, the widespread use of corrective surgery whichrenders corneas unsuitable for grafting, and the severe limitations of currently available synthetic polymer-based artificialcorneas (keratoprostheses). The originality of the proposal lies in the use of recombinant human extracellular matrixproteins to build a nano-engineered scaffold to support growth of the different cell types found in the cornea, cells to bederived from human adult stem cell pools. The development of a reconstructed human cornea will represent a realbreakthrough, allowing diseased or damaged corneas to be replaced by tissue-engineered human corneal equivalentsthat resemble in all respects their natural counterparts. The proposal also responds to impending ED legislation banningthe marketing of cosmetic products that have been tested on animals, using procedures such as the Draize rabbit eyeirritation test. The development of tissue engineered corneas will provide a non-animal alternative which will thereforealleviate animal suffering. The project will lead to a transformation of industry to meet societal needs using innovative,knowledge-based approaches integrating nanotechnology and biotechnology. The project brings together 14 participantswith complementary expertise from 9 different countries, including basic scientists, ophthalmologists and industrialists (3SMEs). Ethical and standardisation aspects will also be included.

Web site: http://www.cornea-engineering.org

Participants:

Coordinator

France

Dr. David John Stuart Hulmes, CNRS, Institut de Biologie et Chimie des Protéines, Lyontel: +33 4 72 72 26 67 fax: +33 4 72 72 26 [email protected]

Belgium• Betty V. Nusgens, University of Liège, Dept. of Preclinical Sciences MI, Faculty of Medicine,

Laboratory of Connective Tissue Biology, Liège

Finland• Eija-Riitta Hamalainen, Fibrogen Europe Oy, Helsinki, SME

France• Jean-Marc Legeais, Assistance Publique - Hôpitaux de Paris, Laboratoire Biotechnologie et Oeil,

Hopital Hotel-Dieu de Paris• Patrick Sabatier, Banque Française des Yeux, Paris• Pascal Bernard, Laboratoires Ioltech, La Rochelle, SME• Eric Perrier, Coletica, R&D Department, Lyon, SME

Germany• Jurgen Bednarz, Universitatsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fur

Augenheilkunde, Hornhautbank

Israel• Efrat Kessler, Tel Aviv Univ., Goldschleger Eye Research Inst., Sackler Fac. Medicine, Tel Aviv

Italy• Paolo Rama, Fondazione Centro San Raffaele del Monte Tabor, Ophthalmology Department San

Raffaele Hospital, Milan• Graziella PELLEGRINI, Fondazione Banca degli Occhi Del Veneto - Epithelial Stem Cell

Laboratory - SS. Giovanni e Paolo Hospital, Venice

Sweden• Ake Oldberg, Lunds universitet, Department of Cell and Molecular Biology, Lund

Turkey• Vasif Hasirci, Middle East Technical University Department of Biological Sciences, Biotechnology

Research Unit, Ankara

United Kingdom• Timothy Newson, University of Dundee, Division of Civil Engineering, Dundee

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G4 Nanosciences andNanotechnologies

SME SUPPLY CHAIN INTEGRATION FOR ENHANCED FULLY CUSTOMISABLEMEDICAL IMPLANTS, USING NEW BIOMATERIALS AND RAPID MANUFACTURING

TECHNOLOGIES, TO ENHANCE THE QUALITY OF LIFE FOR EU CITIZENS

Proposal acronym Custom-IMD EC contribution (€) 5.400.000Contract n° NMP3-CT-2006-026599-2 Instrument IPDuration (starting date) 4 years (01.01.2007) Participants 23

Abstract:

The 2010 industry paradigm will be that the ‘Implantable Medical Device’ surgeon will plan and execute surgicaloperations based solely on the clinical needs of the patient. Custom-IMD will realise this vision through the developmentof new biomaterials for the manufacture of innovative fully customised medical implants using enhanced rapidmanufacturing technologies; achieving implant design, manufacture, sterilisation, regulatory approval and delivery to thesurgeon within a 48 hour time frame.The core project objectives are:- The development of innovative biomaterials (ceramics, bio-passive, bio-active and shape-memory polymers) for use inRapid Manufacturing.- To undertake in-vitro, cell culture and in-vivo animal studies for the new biomaterials; thus generating a strongtoxicological and biocompatibility knowledge base.- To achieve innovations within five Rapid Manufacturing techniques enabling the processing of the selected biomaterialsachieving targeted material properties and timeframe.- To achieve integration of the medically certified e-supply chain management (confidential patient data, material supply,implant design and manufacture, sterilisation and certification) enabling customised implants to be supplied to thesurgeon within 48 hours.- The design, manufacture and testing of three fully customisable implant products (craniofacial bone plate; lumbar spinaldisc replacement; and dental restoration) achieving target implant specifications.- To demonstrate the direct economic savings to the European healthcare service for customisable implants and toquantify their wider economic and societal ‘added value’.The project objectives demonstrate high relevance to the NMP objectives, including: industrial transformation towardshigh-tech / knowledge based processes and products; higher added value (economic competitiveness); the generation ofnew knowledge; and greater European integration (across science, industry and society)

Web site: not yet

Participants:

Coordinator

Spain

Mr Manuel Leon, Ascamm, Parc Tecnològic del Valles, Cerdanyola del Vallès, Barcelona, SMEtel: +34 935 944 700 fax: +34 935 801 [email protected]

Belgium• Michel Janssens, Materialise, Leuven

Germany• Thomas Wiest, Bremer Goldschlägerei Wilh. Herbst GmbH & Co, Bremen, IND• Michael Shellabear, Electro Optical Systems GmbH, Munich, IND• Konrad Wissenbach, Fraunhofer-Institut fur Lasertechnik, Aachen

Poland• Damian Pustelnik, ENTE sp. z o.o., Gliwice, IND• Janusz Marian Rosiak, Centre of Excellence "Application of Laser Techniques and Biomaterials in

Medicine", Lodz

Netherlands• Joost De Bruijn, Progentix, Bilthoven, SME• Anton Bosman, Suprapolix, Eindhoven, SME• Mark Welters, Innalox, Tegelen, SME• Hanneke Boersma, Strategic Medical Consultants, Leiden• Nico F. Kamerman, TNO, Industrie en Techniek, Eindhoven• Jules M.N. Poukens, Academish Ziekenhuis Maastricht, Maastricht

Spain• Vicenc Gilete Garcia, NeoSurgery, Cerdanyola del Valles, SME• Liliana Chamudis-Varan, Aimplas, Paterna-Valencia, SME• Carlos Atienza, IBV, Universidad Politécnica de Valencia, Valencia• Alberto Lombarte, PlastiaSite, Barcelona, SME• Carles Rubies, UDIAT, Barcelona, SME• Pablo Clavel, Sant Pau Hospital, Barcelona

Switzerland• Karl Stadler, Icotec, Altstatten, SME• Kurt Ruffieux, Degradable Solutions, Schlieren, SME

United Kingdom• Habib Hussein, Ideas3, Englefield Green, SME• Emyr Peregrine, Rapra Technology Ltd, Shrewsbury, Shropshire, SME


NOVEL THERAPEUTIC STRATEGIES FOR TISSUE ENGINEERING OF BONEAND CARTILAGE USING SECOND GENERATION BIOMIMETIC SCAFFOLDS

Proposal acronym EXPERTISSUES EC contribution (€) 7.300.000Contract n° NMP3-CT-2004-500283 Instrument NoEDuration (starting date) 5 years (01.10.04) Participants 20

Abstract:

The main aim of the proposed network of excellence (NoE) is to combat and overcome fragmentation of EuropeanResearch on the field of Tissue Engineering of Bone and Cartilage. The network will bring together Europe's leadingacademic centres and several complementary industrial players in a multi-disciplinary consortium to conduct andstructure research that is able to compete in the internationally arena, namely with USA and Japan. The constitution ofthis NoE will lead to a complete restructuring and reshaping of the European research in this field. The size of thenetwork (20 partners from 13 countries, including 9 of the EU member states), and the selection of its original members,was designed in order to join together the critical mass and all the expertises needed to be an unavoidable worldreference on the topic of tissue engineering of bone and cartilage. In order to achieve that, the network also incorporates,as part of an International Advisory Board (not funded by EU), academic partners of leading institutions in the USA,Canada and Singapore. This NoE aims to provide new tissue engineering technologies for therapeutic treatments, whichwill ultimately have a major social impact by contributing to the challenge of providing lifelong health for our society at anaffordable cost. The objective of creating a long lasting structuring effect of the European research on tissue engineeringwill in fact converge with the overall goal of the Network, which is to establish a sustainable Virtual European Centre ofExcellence in Tissue Engineering of Bone and Cartilage that overcomes the fragmentation of European research in thisfield. Network activities will be organized through a Joint Programme of Activities (JPA) structured in three levels: JointProgramme of Integration (JPI), Joint Programme of Research (JPR), Joint Programme of Spreading (JPS) andManagement. The EXPERTISSUES NoE is now focused around 20 core partners that provide the necessary expertiseand resources that realistically can be expected to participate on the joint programme of activities. The NoE will beinitially composed by 131 researchers (including also 147 registered doctoral students), corresponding to an averageannual budget of around 1.83 million €.

Web site: http://www.expertissues.org

Participants:

Coordinator

Portugal

Prof. Rui Luis Reis, 3B´s Research Group - Biomaterials, Biodegradables and Biomimetics, Dept.Polymer Eng., University of Minho, Bragatel: +351 253 604 781 / 2 fax: +351 253 604 [email protected]

Austria• Heinz Redl, Ludwig Boltzmann Institute, LBI Trauma Care, Vienna

Belgium• Wilfried Vancraen, Materialise N.V., Leuven, SME

Czech Republic• Frantisek Rypacek, Acad. Sciences Prague, Dept. Bioanalogous & Biodegradable Polymers

Finland• Pertti Olavi Tormala, Institute of Biomaterials, Tampere University of Technology

Germany• Charles James Kirkpatrick, Johannes Gutenberg-University, Institute of Pathology, Mainz• Nicole Rotter, Dept. Otorhinolaryngology, University Hospital of Schleswig-Holstein, Lübeck• Herma Glockner, CellMed AG, Alzenau, SME

Israel• Daniel Cohn, Casali Institute of Applied Chemistry, The Hebrew University of Jerusalem

Italy• Emo Chiellini, Dept. Chemistry and Industrial Chemistry, University of Pisa• Claudio Migliaresi, Dipt. Ingegneria Materiali e Tecnologie Industriali, Universitá di Trento• Bruno Fiorentino, Kedrion S.p.A., Barga, SME

Spain• Julio San, Roman, Consejo Superior de Investigaciones Científicas, Madrid

Sweden• Paul Gatenholm, Dept. Materials & Surface Chemistry, Chalmers Univ. Technol., Gothenburg

Switzerland• Ralph Müller, Inst. Biomedical Engineering, Swiss Federal Inst. Technology (ETH), Zurich• Jeff Hubbell, Inst. Sci. et ingénierie chimiques, Ecole Polytechn. Féd. de Lausanne (EPFL)

Turkey• Vasif Hasirci, Dept. Biological Sciences, Ankara, Middle East Technical University, Ankara• Erhan Piskin, Dept. Chemical Eng., Bioengineering Division, Hacettepe University, Ankara

United Kingdom• Paul Vincent Hatton, Centre Biomaterials and Tissue Engineering, School Clin. Dentistry,

University of Sheffield• Alicia Jennifer El Haj, Centre Science and Technol. in Medicine, Keele Univ., Stoke-on-Trent


ADULT MESENCHYMAL STEM CELLS ENGINEERINGFOR CONNECTIVE TISSUE DISORDERS. FROM THE BENCH TO THE BED SIDE

Proposal acronym GENOSTEM EC contribution (€) 8.752.000Contract n° LSHB-CT-2003-503161 Instrument IPDuration (starting date) 4 years (01.01.04) Participants 23

Abstract:

The objective of this Integrated Project Genostem is to establish an European international scientific leadership foe stemcell regenerative medicine in the field of connective tissue disorders. Autologous adult Mesenchymal Stem Cells (MSCs)are optimal candidates to serve as the building blocks for the engineering of connective tissues since they are themultipotential stem cells that give rise to skeletal cells (osteoblasts, chondrocytes and tenocytes), vascular cells(endothetial cells, pericytes and vascular smooth muscle cells), sarcomeric muscle (skeletal and cardiac), andadipocytes. To our knowledge, there is no systematic study on the different facets of MSC biology and engineering,which is the precise purpose of this project. Genostem will compare different tissue sources of MSCs and isolate MSCssubsets in order to obtain undifferentiated MSCs, committed MSCs at early stage of differentiation, progeny blocked atspecific differentiation stage and fully differntiated progeny. Genostem will study the complete MSC gene productrepertoire using genomic and proteomic analysis that should provide with the molecules and pathways potentiallyoperative for the maintenance and differentiation of stem cells. Genostem will develop new technologies to generatebiodegradable matrices, scaffolds and microcarriers that bind pharmacologically active proteins and allow their delivery ina controlled way; these biomaterials will allow to engineer MSCs such as to obtain optimal repair of the target injuredtissue. Genostem will improve methods for gene transfer using original lentivirus or non viral delivery systems(polymersomes and matrix-anchoring, DNA-binding peptides) in order to carry out gain (gene transfer) and loss (siRNAtransfer) on function studies. Genostem will develop a number of transplantation models of MSCs mimicking humanpathological processes operative in osteoarthritis, rheumatoid arthritis, bone congenital disease, extented bone factures,osteoporosis, tendon injuries, limb and coronary ischemia, cardiopathy, pulmonary arterial hypertensive disease andcancer. The final goal is to develop clinical trials using MSCs, in bone, cartilage and tendon disorders, in partnership withSMEs and regulatory bodies for the scale up of safe procedures, taking advantage of the experience already acquired byone of the partner in clinicals trials using cultured muscle cells. Genostem brings together a combination of expertises inMolecular Biology, Cellular Biology, Biomechanics, Genomics, Proteomics, Bioinformatics and Molecular Medicine. Thecritical mass achieved by this Consortium that comprises a few hundred researchers from public agencies, universitiesand SMEs, should enable breakthroughs in MSC engineering directly amenable for clinical applications.

Web site: http://www.genostem.org

Participants:

Coordinator

France

Prof. Christian Jorgensen, Institut national de la santé et de la recherche médicale, Montpelliertel: +33 4 67 33 89 63 fax: +33 4 67 33 77 [email protected]

France• Pierre Charbord, Université François Rabelais, Tours• Jacques Hatzfeld, Centre National de la Recherche Scientifique, Villejuif• Jean-Pierre Pujol, Université de Caen• Jean-Pierre Mouscadet, AbCys SA, Paris, SME• Nathalie Rougier, Biopredic International, Rennes, SME• Marielle Maurice, Genopoietic S.A.S., Miribel, SME• Jonathan Dando, INSERM Transfert SA, Paris

Germany• Gerhard Gross, German Research Centre For Biotechnology, Braunschweig• Christian Peschel, Technische Universität Munchen• Ulrike Nuber, Max Planck Society, Berlin• Thomas Haüpl, Charité universitätmedizin Berlin

Greece• Helen Papadaki, University of Crete, Fac. Medicine, Haematology Research Lab., Heraklion• Maria Kalmanti, University of Crete, Fac. Medicine, Pediatric Hematology - Oncology, Heraklion

Israel• Dan Gazit, The Hebrew University of Jerusalem• Erella Livne, Technion - Israel Institute of Technology, Haifa

Italy• Paolo Bianco, Università La Sapienza Roma

Portugal• Nuno M. Neves, University of Minho, Braga

Romania• Virgil Paunescu, University of Medicine and Pharmacy Victor Babes, Timisoara

Spain• Jeronimo Blanco Fernandez, Instituto de Ciencias Cardiovasculares de Barcelona

Swizerland• Ralph Mueller, Swiss Federal Institute of Technology, Zurich• Jason Schense, Kuros Biosurgery, Zurich, SME• Jeffrey A. Hubbell, Swiss Federal Institute of Technology, Ecublens

United Kingdom• Yuti Chernajovsky, Queen Mary & Westfield College, University of London


A HYBRID APPROACH FOR BONE AND CARTILAGE TISSUE ENGINEERING USINGNATURAL ORIGIN SCAFFOLDS, PROGENITOR CELL AND GROWTH FACTORS

Proposal acronym HIPPOCRATES EC contribution (€) 2.896.000Contract n° NMP3-CT-2003-505758 Instrument STREPDuration (starting date) 4 years (01.02.04) Participants 7

Abstract:

This project aims to provide new tissue engineering technologies for therapeutic treatments, which will ultimately have amajor social impact by contributing to the challenge of providing lifelong health for our society at an affordable cost. Themain aim is the development of advanced functional materials that are needed for improved quality of life of thousands ofpatients suffering from cartilage or bone tissue loss or malfunctioning. The improved therapy suggested herein will resultin a decreased morbidity and mortality of patients with reduction of the overall costs in EU healthcare. A major objectiveis the development of tissue engineering (TE) products that can be used for bone TE, cartilage TE or for anosteochondral TE strategy.Natural origin scaffolds mainly based on algae & chitosan will be used for bone and cartilage. Ceramic (bi-phasiccalcium-phosphate) scaffolds will be obtained from mineralised red algae. For the osteochondral approach, specifictechnologies will be developed to produce complex bi-material (polymer/ceramic) constructs. An all range of adequateprocessing techniques to obtain suitable scaffolds will be developed.One of the main innovations will be the development and use of specific software packages for designing patient specificscaffolds that will be combined with the production of the scaffolds by means of 3D plotting methodologies. Othertechniques will include melt based processing and solvent based techniques.The scaffolds will also be loaded with a range of growth factors (GF), including several bone-morphogenetic proteins(BMPs) other GF in the TGF-ß family. Primary cells and progenitor cells obtained from animals and later on from humanpatients will be used to develop the tissue engineered products. Cell culturing methodologies will be optimised andspecific ways of controlling the cultures evolution into the desired phenotypes will be developed. In-vivo functionalityassessment experiments will also be carried out.

Web site: http://www.hippocratesproject.org

Participants:

Coordinator

Portugal

Prof. Rui Luís G. Reis, Universidade do Minho, Bragatel: +351 253 604 781 fax: +351 253 604 [email protected]

Austria• Heinz Redl, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna• Christian Gabriel, Red Cross Transfusion Service of Upper Austria, SME

Belgium• Michel Janssens, Materialise N.V., Leuve, SME

Germany• Mr Hendrik John, Envisiontec GmbH, Marl, SME• C.J. Kirkpatrick, Johannes Gutenberg University of Mainz

United Kingdom• Matthew Dring, Queen's University Belfast


DEVELOPMENT OF NEW POLYMERIC BIOMATERIALSFOR IN VITRO AND IN VIVO LIVER RECONSTRUCTION

Proposal acronym LIVEBIOMAT EC contribution (€) 2.299.906Contract n° NMP3-CT-2005-013653 Instrument STREPDuration (starting date) 3 years (01.04.05) Participants 5

Abstract:

The development of new polymeric biomaterials designed to stimulate specific cellular responses at the molecular levelsuch as activation of signalling pathways that control gene activity involved in maintenance, growth, and functionalregeneration of liver tissue in vitro could be an important step in tissue engineering. The project is aimed to thedevelopment of polymeric synthetic and biodegradable biomaterials to control liver cell responses in vitro and in vivosystems. Isolated hepatocytes are able to continue the full range of known in vivo liver specific functions for only a shorttime. The in vitro maintenance of competent hepatocytes is decidable so that the liver functions can be studied in acontrolled environment. Engineered liver tissue constructs may provide an inexpensive and reliable in vitro physiologicalmodel with great control of variables for studying disease, drug, infection and molecular therapeutics. New modifiedpolyetheretherketone PEEK-WC membranes will be prepared in hollow fibre configurations. Membranes will be preparedby phase inversion technique, which permits to obtain membranes with various structural properties by means of kineticand thermodynamic parameter control. In addition, the development of synthetic polymeric materials consisting ofnanofiber network scaffolds represents an entirely new approach to tissue engineering that has relied in the past onmaterials that where either of unknown composition (i.e. Matrigel) or not possible to design (i.e. Collagens). Thus, thedesign and preparation of synthetic three-dimensional nanofiber network scaffolds that highly mimic the extra cellularmatrix will be a valuable tool in the field. The surface of membranes/scaffolds to be utilized in the project will be modifiedby non equilibrium plasma-chemical processes such as Plasma Deposition of thin films (PE-CVD) and PlasmaTreatments to adapt their properties to the best compatibility with cells. With the same objective, plasma-modifiedsurfaces will be further modified by means of immobilisation reactions of biomolecules able to stimulate specific cellularresponses at the molecular and cellular level.

Web site: http://www.uni-leipzig.de/livebiomat

Participants:

Coordinator

Germany

Prof. Agustinus Bader, University Leipzig, Center for Biotechnology and BiomedicineCell Techniques and Applied Stem Cell Biology, Leipzigtel: +49 (0)341 97-31351 fax: +49 (0)341 [email protected]

Germany• Ulrich Großkinsky, LSMW GmbH, Berlin IND

Italy• Loredana de Bartolo, Inst. Membrane Technology, National Research Council of Italy, Rende• Pietro Favia, University of Bari, Department of Chemistry, Bari

Spain• Carlos E. Semino, Salvador Borrós & Mercedes Balcells, University Ramon Lull, Barcelona

Bioengineering Center, Barcelona


INTELLIGENT NANOCOMPOSITE FOR BONE TISSUE REPAIR AND REGENERATION

Proposal acronym NANOBIOCOM EC contribution (€) 2.017.616Contract n° NMP3-CT-2005-516943 Instrument STREPDuration (starting date) 3 years (01.05.05) Participants 8

Abstract:

There are roughly 1 million cases in the USA and 0.5 million in EU of high skeletal defects a year. All of these casesrequire bone-graft procedures to achieve union, each of which requires the surgeon to determine the type of graftmaterial to be use. The toughest challenge appears when the size of the defect is too big and the reconstruction of thisdefect requires a bone graft capable of supplying similar physical properties and behavior to the bone being substituted.Unfortunately at this moment commercial scaffolds can not satisfy the following issues: 1) To promote new boneformation in order to reduce the time of bone healing and decrease the vascular insult of the implant to the bone andcause less-stress shielding. 2) Mechanical properties that match those of human tissue to be regenerated during its newformation. 3) Large segment of implants. For patients who have lost large segments of bone due to a congenital defect,degenerative diseases, cancer or accident.Based on these basic needs to provide an ideal scaffold, the NANOBIOCOM project aims at establishing the scientificand technological basis for the development new “intelligent” composite scaffold for bone tissue repair and regenerationwith the following issues: 1) Bioactive behavior capable of activating osteoprogenitor cells and genes and within an invivo environment provide the interface to respond to physiological and biological changes, 2) Mechanical and structuralproperties similar to a healthy bone. 3) Size and shape required for reconstructing big skeletal defectsNANOBIOCOM focuses on the development of an intelligent material with the following challenges: 1) The bioactivity ofthe composite, which is rendered by the bioactive components (nanoparticles, carbon nanotubes, polymers) in thecomposite and/or by external stimulation (BMP’s, Electrical Fields, biofunctionalitation) will active osteoprogenitor cellsand gens, and consequently promote the tissue growth adjacent to the implant. 2) Mechanical and structural propertiesof the scaffold equal to a healthy bone synchronous with new bone formation. By the incorporation of nanoparticles ascarbon nanotubes and nanohidroxiapatite into the composite are expected to be highly suitable reinforcement for theimplants of the load bearing structures of our body such as bone and cartilage. 3) The size and shape of biodegradableimplants. We are going made large segments of implants required for reconstructing big defects capable of supplyingsimilar physical properties and behavior of healthy bone to be replaced, in contrast with the small implants that are madeat present. 4) Understanding the genetic programming of bone regeneration. To realize the potential for novel “intelligent”composite materials to serve as scaffolds for bone regeneration requires that the innate programming mechanismsinvolved in bone development and repair are effectively harnessed.The main output of NANOBIOCOM project will be: 1) An appropriate cell bioactive system to initiate repair andregeneration of bone. 2) Intelligent composite for 3D scaffold, which will be able to support physiological loading untilsufficient tissue regeneration occurs and will be possible manufacture large segments. 3) A comprehensive geneexpression profiles of the temporal regulation of gene expression during bone development.

Web site: http://www.nanobiocom.org

Participants:

Coordinator

Spain

Dr. Iñaki Álava & Maria Jesús Jurado, Fundación Inasmet, , Department of Materials andprocesses, Donostia-San Sebastiantel: +34943003700 fax: [email protected]

Italy• Jose M. Kenny, Consorzio Interuniversitario Nazionale pa la Scienza dei Materiali, Department of

Materials Science and Technology, Terni• Gabriela Ciapetti, Nicola Baldini, Donatella Granchi & Elisabetta Cenni, Istituti Ortopedici Rizzoli,

Laboratorio di Fisiopatologia degli Impianti Ortopedici, Bologna

Netherlands• J.A. Jansen, XF Walboomers, JGC Wolke & J van den Dolder, Stichting Katholiek Universiteit,

Department of Periodontology and Biomaterials, Nijmegen

Spain• José L. Peris & Amelia Gómez, Instituto de Biomecánica de Valencia, Implant section, Barcelona• Laureano Simon, Lourdes Osaba & Pilar Saenz, Progenika Biopharma S.A., Derio-Vizcaya IND

Switzerland• Jaques Lemaître, Ecole Polytechnique Federale de Lausanne, Laboratory for Powder

Technology, Lausanne

United Kingdom• Colin McCaig & Ian Gibson, University of Aberdeen, School of medical Sciences, Institute of

medical Sciences, Aberdeen


3G-NANOTECHNOLOGY BASED TARGETED DRUG DELIVERYUSING THE INNER EAR AS A MODEL TARGET ORGAN

Proposal acronym NanoEar EC contribution (€) 10.499.957Contract n° NMP4-CT-2006-026556 Instrument IPDuration (starting date) 4 years (01.11.2006) Participants 23

Abstract:

The goal of the NANOEAR consortium is to develop novel multifunctional nanoparticles (MFNPs), which are targetable,biodegradable, traceable in-vivo and equipped with controlled drug release. With over 44 million EU citizens with treatablehearing loss, and 40 000 profoundly deaf who can be benefit with MFNP-based novel cochlear implant, the inner ear is aunique target. Both a model for nervous system disorders and difficult-to-access body sites; it is isolated, with neural andvascular targets, and is immuno-privileged. Measures of function and structure are quantitative and precise. Highlypenetrating delivery vehicles will be created to carry and release drugs precisely to targeted tissue sites and selectedcells. Nanoparticles, dendrimers, micelles and polymer-protein complexes will be designed for delivery of drugs/genes toselected targets of the inner ear. Four EU/FDA approved degradable biomaterials will be tested for targeting, coating,toxicity and payload carrier capacity. Commercially available liposomes, encapsulated by polyethylene glycol (PEG),impregnated with drugs, and modified with targeting ligands and signalling molecules (gadolinium) will be assessed forbenchmarking purposes. The fabricated MFNPs will be applicable to wide variety of drugs (e.g. conventional therapeutics,growth factors, proteins, nucleic acids, steroids). We will demonstrate greater selectivity, reduced side effects and greaterefficacy than possible with current drug delivery, and provide treatments not currently possible. As a demonstrationmilestone this IP will produce a novel human cochlear implant promoting improved cochlear nerve-implant integration. Inthis demonstration the implant will include a MFNP drug reservoir providing continuous drug delivery and MFNP electrodecoatings providing targets for nerve growth.

Web site: not yet

Participants:

Coordinator

Finland

• Prof. Ilmari Pyykkö, Depart. Otolaryngology, Medical Faculty, University of Tampere, Tampere tel: +358 3 31166387 fax: +358 3 31164366

[email protected]

Austria• Annelies Schrott-Fischer, Medizinische Universität Innsbruck, Innsbruck• Claude Jolly, MED-EL Elektromedizinische Geräte GmbH, Innsbruck, SME

Czech Republic• Josef Syka, Institut of Experimental Medecine, Academy of Sciences of Czech Republic, Prague

Denmark• Marlene Rugaard Jensen, NsGene A/S, Ballerup, SME

Finland• Prof. Minna Kellomäki, Technical University of Tampere, Tampere• Prof. Jarl Björn Rosenholm, Abo Akademi University, Depart. Physical Chemistry, Turku / Abo• Prof. Paavo Kinnunen, Helsingin Yliopisto, Helsinki

France• Patrick Saulnier, University of Angers, Angers• Jean-Luc Puel, Institut National de la Santé et de la Recherche Médicale, UMR 583, Montpellier

Germany• Thomas Lenarz, Medizinische Hochschule Hannover, Hannover• Klaus-Peter Schmitz, Universität Rostock, Rostock• Martin Möller, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Aachen• Joachim Spatz, Ruprecht-Karls-Universität Heidelberg, Heidelberg• Volker Faust, Hemoteq GmbH, Würselen, SME

Greece• Elias Lianos, National and Kapodistrian University of Athens, Athens

Italy• Alessandro Martini, Consorzio Ferrara Ricerche, Ferrara• Paolo Pinton, Aequotech S.R.L, Ferrara, SME

Sweden• Mamoun Mohammed, Kungliga Tekniska Högskolan, Stockholm• Helge Rask-Andersen, Uppsala Universitet, Uppsala

Switzerland• Harm-Anton Klok, Ecole Polytechnique Fédérale de Lausanne, Lausanne

United Kingdom• Victor Hugh Perry, University of Southampton, Southampton• Slava Pavlovets, Yorkshire Bioscience Limited, York, SME

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G4 NS&NT

DEVELOPMENT OF LOAD-BEARING FIBRE REINFORCEDCOMPOSITE BASED NON-METALLIC BIOMIMETIC BONE IMPLANTS

Proposal acronym NEWBONE EC contribution (€) 4.400.000Contract n° NMP3-CT-2006-026279-2 Instrument IPDuration (starting date) 4 years (01.11.2006) Participants 16

Abstract:

The aim of NEWBONE is to develop fibre reinforced composite (FRC) material load-bearing implant: to produce atprototype level two resorbable fixation devices in knee/shoulder ligament repair and twp non-resorbable bone fixationdevices for reconstruction of large bone defects and study the use of developed technologies in complete implants (hipstem, knee) and spine applications. The proposal is high tech SME driven: they represent all the different competenceareas needed to develop FRC bone implant. Research institution partners are adding to the competence portfolio andthe latest knowledge developed by them is transferred to the use of SMEs. Three major breakthrough innovations arepresent in the proposal: FRC material is used for load bearing bone implants; bioactive glass and hydroxyapatite is usedon the implant-bone interface; a new processing method is applied to allow in-situ modifications of the implant duringsurgery. The results will cover the gaps that exist in Europe in terms of increased healthcare costs and decreased qualityof life of patients as well as of Europe dragging behind US in commercialisation of biomaterials and implant technologies.FRC material will reduce problems caused by stresshielding of currently used metal implants. Use of bioactive glass andhydroxyapatite will foster bone growth and implant attachment. The surface structure will allow for inclusion of drugrelease functions to prevent infections. Partners include Swiss SME Medacta International SA, producer of hip and kneeprosthesis and Finnish company ConMed Linvatec Biomaterials Ltd, producer of sport injury repair systems, bothcommitted to the development of FRC implants to be included to their future product portfolios. Together with allindustrial partners involved, the consortium will have the abilities to increase the turnover of European implant industryand take the role of a global leader in the niche sector of FRC load-bearing bone implants.

Web site: not yet

Participants:

Coordinator

Finland

Prof. Pekka Vallittu, Institute of dentistry, University of TurkuDr Saara Lampelo, Business & Life Sci. Turku Polytechnic & AcasiaTrade Ltd Oy, Helsinki, SMEtel: +358-400666366 fax: [email protected]

Belgium• Dirk Drees, FALEX Tribology NV, Rotselaar

Finland• Kaj Koskinen, ConMed Linvatec Biomaterials Ltd, Tampere, SME• Matti K. Viljanen, University of Turku, Department of Prosthetic Dentistry and Biomaterials

Science - Orthopaedic Research Unit, Turku Biomaterials Centre, Turku

France• José Alcorta, Rescoll Technological Centre, Pessac

Greece• Michalis Vardavoulias, PyroGenesis SA, Lavrion, SME

Italy• Luigi Paracchini, Ingeo SNC, Varallo Pombia, SME• Sergio Paoletti, University of Trieste• Gianluigi Carlini, Integra S.r.L., Trieste, SME• Diego Basset Materialia S.r.L, San Vendemiano, SME

Spain• Javier Menendez Medina, NanoBioMatters S.L., Paterna, Valencia, SME• Miguel Angel Munarriz Casajus, AIN – Centre of Advanced Surface Engineering, Cordovilla-

Pamplona

Sweden• Lena Nordholm, University College of Borås, School of Engineering, Polymer technology, Boras

Switzerland• Alberto Siccardi, Medacta International SA, Castel San Pietro, SME• Thomas Hinderling, Swiss Centre for Electronics and Microtechnology, Neuchatel

United Kingdom• Edna Murphy, University of Cambridge


DEVELOPMENT AND EVALUATION OF MINERALIZED SILK BASED COMPOSITESFOR ORTHOPAEDIC APPLICATIONS

Proposal acronym SILKBONE EC contribution (€) 1.599.304Contract n° COOP-CT-2005-18060 Instrument SME-Coop. ResearchDuration (starting date) 2 years (01.10.05) Participants 8

Abstract:

The consortium seeks to develop a highly novel bone substitute material (BSM) from mineralised silk composites for usein medical procedures requiring bone tissue replacement. Spinox have developed Spidrex, a novel silk-silk compositebased on a fibre and matrix generated from spider silk analogues. Spidrex is biocompatible, bio-absorbable and hasexcellent mechanical properties and cell adhesiveness. Pilot studies at Bristol have shown it is rapidly and heavilymineralised by the component of natural bone, hydroxyapatite. Mineralised Spidrex will be developed into a BSM byincorporating osteoinductive factors in the silk matrix and biochemical tailoring both fibre and matrix. Progentix willdevelop non-foetal stem cell technology with which to seed the BSM. 3H Biomedical and U Kon InPuT will test humancell reaction to BSM in vitro. This will reduce the need for animal trials and allow material modification early in the designprocess. Soton will optimise bone formation in the BSM in vitro. A cellularised, load bearing, resorbable BSM isunprecedented and will provide entry to a market estimated at 2.5 billion euros. It will be particularly advantageous forthe treatment of fractures resulting from osteoporosis and bone lesions in cancer patients. The consortium comprises 3highly innovative, research based SMEs from 3 member states whose competitiveness will be enhanced by access tothis market and by collaboration with the consortium's 5 leading RTDs. Individually, each SME does not have thecapability to pursue a project of the above magnitude. Tissue engineering, adult stem cell research and implantablebiomaterials have been flagged as future growth markets, keenly pursued in the U.S. and Asia. Developing know-how inthese areas, and subsequent dissemination of results in Europe will increase E.U. competitiveness in these burgeoningsectors.

Web site: http://www.silkbone.org

Participants:

Coordinator

United Kingdom

Dr. Nick Skaer, Oxford Biomaterials Ltd., Newbury, SMEtel: +44 (0)1635 237226 fax: +44 (0)1635 [email protected]

Germany• Sonja Von Aulock, Center for Health and Consumer Protection, Technology Transfer Center for in

vitro Pharmacology and Toxicology, Universitat Konstanz

Netherlands• Joost Dick De Bruijn, Progentix BV i.o., Bilthoven, SME

Sweden• Wilhelm Engstrom, Department of Biosciences and Veterinary Public Health, Sveriges

Lantbruksuniversitet, Uppsala• Bror Morein, 3H Biomedical AB, Uppsala, SME

United Kingdom• Stephen Mann, school of Chemistry, University of Bristol• Fritz Vollrath, department of Zoology, University of Oxford• Helmtrud Isolde Roach, Bone and Joint Research Group, Southampton General Hospital,

University of Southampton

Commission: Directorate General for Research - Implementation of activities to outsource Directorate - Unit T4 SMEs

INJECTABLE MACROPOROUS BIOMATERIALBASED ON CALCIUM PHOSPHATE CEMENT FOR BONE REGENERATION

Proposal acronym SmartCaP EC contribution (€) 1.796.814Contract n° NMP3-CT-2005-013912 Instrument STREPDuration (starting date) 3 years (01.05.05) Participants 7

Abstract:

Osteoporosis and bone degeneration in aging populations as well as bone defects caused by trauma and pathologygrounds a societal need for therapeutic products. The main goal and the breakthrough of this project are to implement anovel concept of biomaterials for bone regeneration, with a range of properties that elicit specific cell responses. Thebiomaterials developed in this project will give improvements in health, quality of life, environment and safety. Thesemultifunctional biomaterials will be injectable, porous, intelligent and biodegradable to promote osteogenesis andangiogenesis. Because these biomaterials will be injectable, they will be applied by means of minimally invasive surgery.This means less suffering by the patient, reduction of health care cost, simple surgical technique and improved workingconditions. These biomaterials will be an advantageous alternative to autologous bone due to their large availability andthat they can be obtained sterilized right off the shelf.

Web site: http://www.smartcap.eu

Participants:

Coordinator

Spain

Prof. Josep A. Planell, Technical Univ. Catalonia, Dpt. Materials Science & Metal. Eng., Barcelonatel: +34 934 011 612 fax: +34 934 016 [email protected]

Belgium• Etienne Schacht, University of Ghent, Department of organic Chemistry/Polymer materials

research group, Ghent

Germany• Lutz Claes, University of Ulm, Institut fuer Unfallchirurgische Forschung und Biomechanik, Ulm

Ireland• Patrick Prendergast, Trinity College Dublin, Centre for Bioengineering, department of mechanical

engineering, Dublin

Italy• Luigi Ambrosio, Consiglio Nazionale delle Richerche, Institute of Composite and Biomedical

Materials, Roma• Nicola Baldini, Instituti Ortopedici Rizzoli, Laboratorio di Fisiopatologia degli Impianti Ortopedici,

Bologna

United Kingdom• Matteo Santin, University of Brighton, School of Pharmacy and Biomolecular Sciences, Brighton


A SYSTEMS APPROACH TO TISSUE ENGINEERING PROCESSES AND PRODUCTS -BIOMATERIAL ENGINEERING BIOMEDICAL ENGINEERING NANOTECHNOLOGY

Proposal acronym STEPS EC contribution (€) 13.063.154Contract n° NMP3-CT-2005-500465 Instrument IPDuration (starting date) 4 years (01.03.05) Participants 23

Abstract:

Tissue engineering (TE) is a rapidly emerging field aimed at the regeneration of tissues and organs for the treatment ofdisease and injury. TE is based upon scaffold-guided tissue regeneration, and involves the seeding of porous,biodegradable scaffolds with donor cells, the culture of the resulting biohybrid construct in vitro with or without the use ofgrowth factors and finally the implant of the construct into the patient to induce and direct the growth of new healthytissue. Current clinical applications of tissue-engineered constructs include engineering of skin, cartilage and bone forautologous implantation. Whilst some technological and clinical success has already been achieved, thus demonstratingthe potential for TE to make a significant impact on healthcare, there has been a marked lack of connectivity betweendifferent components in TE such as the technological development, the industrial up-scaling, the European regulatorypanorama, the ethical consideration, the public awareness and the socio-economical validation. Based upon thehypothesis that the only way to successfully implement TE is to systematically link together all aspects of thismultidisciplinary process, STEPS is designed to fill those gaps that presently limit the full exploitation of TE. STEPSaddress this by introducing a systems approach to TE-related issues to reach an integrated network of TE-relatedknowledge. Such knowledge-based research is designed to address four distinct applications of tissue engineering, eachof which is at a different stage of development and therefore lends itself to different pre or post-commercializationanalyses. Specifically, the technological components of the Project will include novel biomaterial development, cellsourcing and manipulation, bioreactor design and the integration of TE constructs into the living host. The programmeincludes the evaluation of the socio-economic issues related to ethics and health economics. This will include anassessment of the public acceptability of these emerging technologies and the ability of private and public healthinsurances to efficiently balance innovation and cost containment. The Consortium has therefore put together anobjective-driven approach, designed to deliver radical innovations in the long term as well as new processes,methodologies and products in the short and medium term. The current potential world market for TE products isestimated at €100 billion but a poorly integrated infrastructure will be incapable of delivering to this market. We believethat this approach will positively transform the European industrial infrastructure related to the development of TissueEngineered products and processes and lead to significant benefits for the public.The Consortium comprises 23 partnersfrom 13 European countries. It includes 6 industrial organisations, 4 of whom are SMEs and 17 academic centres. Inorder to tackle the development of such a highly innovative systems approach to TE, the contribution of a truly multi-disciplinary Consortium, of a critical mass in man power, and of substantial financial commitment, is required. Thesemultidisciplinary skills are indeed found only within a European cooperation and all the partners are internationallyidentified centres of excellence in their respective areas of expertise.

Web site: http://www.stepsproject.com

Participants:

Coordinator

Italy

Ms Alessandra Pavesio, FAB - Fidia Advanced Biopolymers S.r.l., Abano Terme, INDtel: +39 04 982 328 88 fax: +39 04 982 325 57E-mail : [email protected]

Austria• Stefan Nehrer, University of Vienna

Belgium• Joseph Selling, Katholieke Universiteit Leuven

France• Michel Therin, Sofradim Production, Trevoux, SME• Jean Pierre Boutrand, Biomatech, Chasse sur Rhône, SME

Finland• Pertti Olavi Tormala, Institute of Biomaterials, Tampere University of Technology

Germany• Lutz Claes, University of Ulm• Michael Sittinger, Medical Faculty Charité Humboldt-University of Berlin

Ireland• Peter McHugh, National University of Ireland, Galway

Italy• Luigi Ambrosio, Consiglio Nazionale delle Ricerche, Roma• Giuseppe Remuzzi, Istituto di Ricerche Farmacologiche Mario Negri, Milano• Maurilio Marcacci, Istituti Ortopedici Rizzoli, Bologna

Latvia• Garry Kerch, Riga Stradins Unversity

Netherlands• Jan Feijen, University of Twente, Enschede• Jaap Oostra, Applikon Dependable Instruments B.V., Schiedam, SME

Poland• Malgorzata Lewandowska, Warsaw University of Technology

Spain• Josep Anton, Planell, Universitat Politècnica de Catalunya, Barcelona

Sweden• Lars Hedman, Cell Matrix AB, Gothenburg, SME• Anders Lindahl, Goeteborg University

Switzerland• Ivan Martin, University of Basel

United Kingdom• Julian Braybrook, LGC Limited, Teddington, IND• David Williams, University of Liverpool• Richard Lilford, University of Birmingham• Anthony Peter Hollander, The University of Bristol


BIOREACTIVE COMPOSITE SCAFFOLD DESIGNFOR IMPROVED VASCULAR CONNEXION OF TISSUE-ENGINEERED PRODUCTS

Proposal acronym VASCUPLUG EC contribution (€) 2.300.000Contract n° NMP3-CT-2005-013811 Instrument STREPDuration (starting date) 3 years (01.04.05) Participants 8

Abstract:

Engineered tissues today in most cases lack of appropriate connexion to the vascular system of the surrounding tissue inthe body at the implantation site. Hence the tissues suffer from malnutrition and low gas exchange leading to necrosis.To overcome this bottleneck the strategic objective of this project is to develop a novel threedimensional scaffoldstructure for improved vascularisation of tissue-engineered products.Application of intelligent biomaterials (bioresorbable stimuli-sensitive polymers) and incorporation of bioactive substances(e.g. growth factors) will enhance a structured vascularisation of tissue-engineered constructs by gradually openinginserted microchannels for vessel ingrowth into cellseeded polymeric scaffolds. Furthermore, the mechanism of inductionof secondary angiogenesis by monocytes can be used to promote vascularisation. The signal for the stimulus-sensitivepolymer to act (meaning: induction of angiogenesis) is intended to be a pH drop associated with malnutrition of cells. Theuse of angiogenic factors in promoting vascularisation of tissue-engineered constructs so far was performed by a ratherisotropic distribution of factors in the scaffolds preventing the buildup of a gradient of bioactive substances for directedcell growth (angiogenesis). In our approach stimuli-sensitive materials which are available will be tested for theirapplication as switching filaments to open microchannels and guide cells involved in vascularisation and/or provide agradient for directed cell migration and growth. The composite scaffold giving rise to evolving vessels is intended to allowthe vascular connexion to the surrounding tissue in the course of wound healing.The complex bunch of requirements for a functional vascularisation of tissue-engineered products calls for a strong inter-and transdisciplinary co-operation of chemists, biologists, engineers, physicists and physicians depending on apronounced cross-frontier collaboration.

Web site: http://www.gkss.de/euprojekte/PSP6_FP6/VASCUPLUG.html

Participants:

Coordinator

Germany

Dr. Barbara Seifert, GKSS Forschungszentrum, Geesthacht GmbH, Institut für Chemie, Teltowtel: +49 3328 352 482 fax: +49 3328 352 [email protected]

Germany• Gudrun Knedlitschek, Karl-FriedrichWeibezahn & Alexander Welle, Forschungszentrum Karlsruhe

GmbH, Institut für Biologische Grenzflächen, Karlsruhe• Peter Schenck, Dr. Suwelack Skin & Health Care AG, Billerbeck

Greece• Yannis F. Missirlis, University of Patras, Bioengineering Lab, Patras

Hungary• György Kéri & Richard Schwab, Semmelweis University Budapest, Cooperative Research Centre,

Budapest

Spain• María José Alonso, University of Santiago de Compostela, Department de Darmacia e Tecnoloxa

Farmaceutica, Faculty of Pharmacy, Santiago de Compostela

Sweden• Yihai Cao, Karolinska Institutet, Microbiology and Tumour Biology Centre, Stockholm

United Kingdom• David Grant, University of Nottingham, School of MMME, Nottingham


MODELLINGMathematical & biological models, alternatives to animal testing

IN VITRO NEURAL TISSUE SYSTEM FOR REPLACEMENTOF TRANSGENIC ANIMALS WITH MEMORY / LEARNING DEFICIENCIES

Proposal acronym ARTEMIS EC contribution (€) 1.985.420Contract n° LSHB-CT-2006-037862 Instrument STREPDuration (starting date) 3 years (01.03.07) Participants 8

Abstract:

The project concerns the design, development and optimisation of an in vitro system to replace the animalexperimentation in pharmacology and toxicology on neural tissues and in particular on memory and learning. The in vitrosystem will consist of a three-dimensional neural tissue, based on a hydrogel layer bearing neurons generated frommouse embryonic stem cells. The hydrogel layer will be interfaced with multielectrode arrays for electrical stimulation andrecording purposes.Our objective is to use in vitro developed neural tissues instead of transgenic animals carrying memory and learningdeficiencies and, for this reason, our system will be formed by mutated cell lines. Our approach will replace the use oftransgenic animals or (at least) provide preliminary information at the tissue level to orient the design of the transgenicanimals towards the optimal ones decreasing this way the number of animals that are currently created (and sacrificed) bytrial-and-error methods.In addition the system will be used in neurotoxicity tests to correlate measurements at sub-cellular, cellular and synapticnetwork levels as an integrated set with ¿in vivo¿-like effects on in vitro memory/learning, setting the methodological basisfor the design of complementary in vitro tests needed to predict human hazards.The partners of the ARTEMIS constitute an effective consortium that includes experimental and computational biomedicaland biomaterial specialists along with animal experiments labs and standards professionals in this field. The SMEsparticipation in the ARTEMIS project is significant due both to the importance of their contribution at scientific andtechnological level but also to the important benefits they will obtain from the outcomes of the project.

Web site: not yet

Participants:

Coordinator

Spain

Prof. Panetsos Fivos, Departamento de Matematica Aplicada, Universidad Complutense DeMadrid, Madridtel: +34 913946900 fax: +34 [email protected]

Belgium• Kotzias Dimitrios, Institute for Health and Consumer Protection, Joint Research Centre, Ispra

(Va), Bruxelles

Czech Republic• Daniel Horak, Department of Bioanalogous and Special Polymers, Group of Polymer Particles,

Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague

Estonia• Eero Vasar, Department of Physiology, University of Tartu, Visgenyx, Tartu, SME

Hungary• Andras Janos Dinnyes, BioTalentum Ltd., Godollo, SME• George Szekeres, Laboratory of Histopathology, Histopathology Ltd., Pécs, SME

Italy• Novellino Antonio, eTT - Electronic Technology Team, Genova, SME

Poland• Janusz Marian Rosiak, Institute of Applied Radiation Chemistry, Lodz


DEVELOPMENT OF A HIGH THROUGHPUT GENOMICS-BASED TESTFOR ASSESSING GENOTOXIC AND CARCINOGENIC PROPERTIES

OF CHEMICAL COMPOUNDS IN VITRO

Proposal acronym CARCINOGENOMICS EC contribution (€) 10.440.000Contract n° LSHB-CT-2006-037712 Instrument IPDuration (starting date) 5 years (01.11.06) Participants 20

Abstract:

The major aim of CARCINOGENOMICS is to develop in vitro methods for assessing the carcinogenic potential ofcompounds, as an alternative to current rodent bioassays for genotoxicity and carcinogenicity. The major goal is todevelop a battery of mechanism-based in vitro tests accounting for various modes of carcinogenic action. These tests willbe designed to cover major target organs for carcinogenic action e.g. the liver, the lung, and the kidney. The novel assayswill be based on the application of "omics" technologies (i.e. genome-wide transcriptomics as well as metabonomics) torobust in vitro systems (rat/human), thereby also exploring stem cell technology, to generate "omic" responses from awell-defined set of model compounds causing genotoxicity and carcinogenicity. Phenotypic markers for genotoxic andcarcinogenic events will be assessed for the purpose of anchoring gene expression modulations, metabolic profiles andmechanism pathways. Through extensive biostatistics, literature mining, and analysis of molecular-expression datasets,differential genetic pathways will be identified capable of predicting mechanisms of chemical carcinogenesis in vivo.Furthermore, generated transcriptomic and metabonomic data will be integrated into a holistic understanding of systemsbiology, and applied to build an iterative in silico model of chemical carcinogenesis. Subsequently, predictive geneexpression profiles, typically consisting of some 150-250 genes, will be loaded onto high throughput dedicated DNA-chips,thus accelerating the analysis of transcriptomic responses by a factor of 100. It is expected that the outcome of thisproject will generate a platform enabling the investigation of large numbers of compounds for their genotoxic andcarcinogenic potential, as envisaged under the REACH initiative. This will contribute to speeding the identification ofpotential harmful substances to man, while lowering costs and reducing animal tests.

Web site: not yet

Participants:

Coordinator

Netherlands

Prof. Jos Kleinjans, Health Risk Analysis and Toxicology (GRAT), Maastricht Universitytel: +31-43-3881096 fax: [email protected]

Austria• Paul Jennings, Department of Physiology and Medical Physics, Division of Physiology, Renal

Physiology, Innsbruck Medical University, Innsbruck

Belgium• Raffaella Corvi, Institute for Health and Consumer Protection / European Centre for Validation of

Alternative Methods, European Commission - DG JRC, Ispra (Italy), Brussels• Arthur van Iersel, ECOPA-BOARD, European Consensus Platform for Alternatives, Brussels• Vera Maria Rogiers, Department of Toxicology Dermato-Cosmetology and Pharmacognosy,

Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel

Denmark• Erwin Roggen, Department of Pharma-Protein Development, Novozymes AS, Bagsvaerd, IND

France• Christophe Chesne, BIOPREDIC INTERNATIONAL, Rennes, SME

Germany• Susanna-Assunta Sansone, European Bioinformatics Institute (EBI), Microarray Informatics

Team, European Molecular Biology Laboratory, Cambridge (UK), Heidelberg• Ralf Herwig, Max Planck Institute for Molecular Genetics, Department of Vertebrate Genomics,

Max Planck Society, Berlin

Ireland• Michael P. Ryan, UCD School of Biomolecular and Biomedical Science, Conway Institute,

National University of Ireland, Dublin

Netherlands• John P. Groten, Business Unit Physiological Sciences, TNO Quality of Life, Netherlands

Organisation for Applied Scientific Research, Zeist, Delft• Tim Kievits, Research Institute NUTRIM, PamGene International B.V., s-Hertogenbosch, SME• Jan Boei, Department of Toxicogenetics, Leiden University Medical Center, Leiden

Spain• José Castell, Research Center, Fundacion Hospital Universitario La Fe, Valencia• Myriam Fabre, Advanced in vitroCell technologies, Barcelona, SME

Sweden• Petter Björquist, Cellartis AB, Gothenburg, SME

Switzerland• Andreas Hohn, Genedata AG, Basel, SME

United Kingdom• Paul Carmichael, Safety and Environmental Assurance Centre, Unilever, Bedfordshire, IND• Edward Lock, School of Biomolecular Sciences, Liverpool John Moores University, Liverpool• Hector Keun, Biological Chemistry, Division of Biomedical Sciences, Imperial College London


DEVELOPING A VIRTUAL AND MOLECULAR CONTROL BOARDFOR DIVERTING CANCER STEM CELL TO NON-MALIGNANCE

Proposal acronym CONTROL CANCER STEM EC contribution (€) 1.499.892Contract n° FP6-2003-NEST-B1-12930 Instrument NEST-ADVENTUREDuration (starting date) 3 years (01.10.05) Participants 4

Abstract:

Over the past few years, evidence has accumulated supporting the hypothesis that cancer robustness may be attributedto a small portion of the tumour mass, the cancer stem cells (CSCs). This leads us to propose a more target-orientedtreatment for cancer. Our approach is geared towards the addition of Master Switch factors in the microenvironment ofthe CSCs that will lead to their differentiation into non-proliferative and non-malignant cells. These master switch factorsare normally present in the normal stem cell niche to regulate homeostasis.Our proposal is subdivided in in vitro studies, in silico modelling and in vivo testing (transplantation in animal models) ofstem cells representing two types of solid tumours: brain and breast cancers. To achieve our goal, the master switchfactors will be identified and delivered locally, in and around the tumour. For that purpose, we will use microbeads loadedwith the Master Switch protein(s) to deliver, only locally, a high concentration of the differentiating factor(s), recreating anormal microenvironment. Since it relies on the addition of proteins in the environment of the cancer stem cells, we willuse a lab-on-chip system to cultivate and study a small number of CSCs in a controlled microenvironment.Finally, it is known that not all tumours even of a same type respond in the same way or at the same speed to anidentical treatment. We therefore propose to develop biomathematical models of the behaviour of the CSCs based onparameters identified first in vitro and later in vivo. This biomodelisation will help generating the control board, a realisticpredictive model aiming at the custom-tailoring of the tumour treatment.We will then be able to propose a conceptually novel treatment that will include an approach, the facilitation of CSCdifferentiation, an evaluation method using biopsies in combination with the lab-on-chip and detailed treatmentprocedures based on predictions by the control board.

Web site: http://we.vub.ac.be/~cege/leyns/collaborations.html#ccs

Participants:

Coordinator

Belgium

Prof. Luc Leyns, Vrije Universiteit Brussel, Department of Biology, Lab of Cell Genetics, Brusselstel: +32 2 629 3443 fax: +32 2 629 [email protected]

Germany• Claus Duschl, Department of Cellular Biotechnology and Biochips (IMBT), Fraunhofer Institute of

Biomedical Engineering, Munchen

Israel• Zvia Agur, Institute for Medical Biomathematics, Bene Ataroth

United Kingdom• Robert B. Clarke, Dept. of Medical Oncology Breast Biology Group, University of Manchester


REDUCING ANIMAL EXPERIMENTATION IN DRUG TESTING BY HUMANCARDIOMYOCYTE IN VITRO MODELS DERIVED FROM EMBRYONIC STEM CELLS

Proposal acronym INVITROHEART EC contribution (€) 2.701.611Contract n° LSHB-CT-2007-037636 Instrument SME-STREPDuration (starting date) 3 years (01.01.07) Participants 9

Abstract:

The objective of the proposal is to establish stable cell lines that reliably reflect human cardiomyocyte properties by thedevelopment of models derived from human embryonic stem cells. The aim is to deliver reliable in vitro models that couldbe used by the pharmaceutical industry to replace experimental animals in: (1) investigations on pharmacological toxicityand safety of compounds in the drug discovery and development processes, and (2) the testing of toxic effects ofchemicals according to the new system of the Community on the Registration, Evaluation and Authorisation of Chemicals(REACH). In the pharmaceutical industry reliable in vitro cell models would contribute to replace current techniques withanimal experimentation in the selection and optimisation of lead compounds and in documentation of a selected drugcandidate before it enters clinical phases. In the toxicity testing of chemical substances replacement of animal testingmethods can be attained as well.The means to accomplish the objective are in addition to new stable human embryonic stem (hES) cell derivedcardiomyocytes, (1) state of the art methods for electrophysiological cardiac cell monitoring, (2) optical micro-sensormonitoring in micro-cultivation systems for in vitro screening, (3) a multi-micro-bioreactor platform for high-throughputscreening of drugs and chemicals. Comparative studies of cardiomyocytes derived from hES cells with established in vitromodels will be carried out in order to validate the new models and methods.The outcome of the project is new efficient in vitro pre-validation models which will significantly reduce animalexperimentation for cardiotoxicity testing by 60-80%. Furthermore, it will strengthen the possibility for the participatingSMEs to market new potential products in the areas of in vitro assay methods and in vitro compound screening. TheSMEs part in this proposal is substantial and the share of the requested budget for the SMEs is 59%.

Web site: http://www.invitroheart.org

Participants:

Coordinator

Sweden

Prof. Carl-Fredrik Mandenius, IFM Biotechnology, Linköping University, Linköpingtel: +46 13 288967 fax: +46 13 [email protected]

Belgium• Susanne Bremer, Institute for Health & Consumer Protection, European Centre for the Validation

of Alternative Methods, European Commission, DG Joint Research Centre, Ispra, Brussels

Denmark• Morten Laursen, Department 856, Safety Pharmacology, H. Lundbeck A/S, Valby, IND

Germany• Karl-Heinz Boven, Multi Channel Systems MCS GmbH, Reutlingen, SME• Christine Batzl-Hartmann, Pharmacelsus GmbH, Saarbrücken, SME• Achim Stangelmayer, PreSens Precision Sensing GmbH, Regensburg, SME• Elmar Heinzle, Biochemical Engineering, Universität des Saarlandes, Saarbrücken

Sweden• Peter Sartipy, Cellartis AB, Göteborg, SME• Anders Lindahl, Department of Clinical Chemistry & Transfusion Medicine, Göteborgs Universitet,

Göteborg


MODELING, MATHEMATICAL METHODS AND COMPUTER SIMULATIONOF TUMOUR GROWTH AND THERAPY

Proposal acronym M3CS-TU TH EC contribution (€) 2.942.447Contract n° MRTN-CT-2003-044914 Instrument Marie-Curie RTNDuration (starting date) 4 years (01.06.2004) Participants 12

Abstract:

Tumor evolution is a very complex process, involving many different phenomena, which occur at different scales. Fromthe modelling point of view there are three natural scales of interest: the sub-cellular scale, the cellular scale and themacroscopic scale. The main objective of the project is to organise human capital, activities, structures, management incommon to develop mathematical models, algorithms, and computer software for the simulation of multiscale modeling incancer. The successful development of the project requires a synergy of research efforts and knowledge of mathematics,biology, medicine, computer science, chemistry, and physics. In addition, it requires the development of different phasesreferring to the modelling process: phenomenological observation, mathematical modelling, mathematical methods,simulation, prediction, experiments, model validation and refinement. The development of all this requires aninterdisciplinary approach. The objectives are: 1. Developing the whole modeling process from phenomenologicalobservation to simulation and validation, through the design of mathematical models and their qualitative and quantitativestudy, in order to simulate tumour evolution within the full range of scales: from sub-cellular to macroscopic. 2. Linking allabove approaches, in order to gain deeper insight into the dynamics of tumour growth. 3. Developing predictive,quantitative mathematical models which can be used by clinicians in the fight against cancer as a support toexperimental research. 4. Modeling the action of specific therapies to combat cancer, e.g. control of angiogenicphenomena, activation of the immune response, application of chemotherapeutical actions. 5. Developing computationalschemes and simulation tools for the benefit of users active in immunology, cell biology, and medicine who are notnecessarily expert in mathematics or computer sciences. The design of specific simulation tools can be a very usefulbridge between applied mathematicians and bioscientists and can help reducing lab experiments and optimisingotherwise frustrating therapies.

Web site: http://calvino.polito.it/~mcrtn

Participants:

Coordinator

Italy

Dr. Nicola Bellomo, Dipartimento di Matematica, Politecnico di Torino, Torinotel: +39 0115647514 fax: +39 011 [email protected]

France• Claude Verdier, Laboratoire de Spectrometrie Physique, Universite Joseph Fourier, Grenoble• Benoit Perthame, Dept. de Mathematiques et Applications, Ecole Normale Superieure, Paris

Germany• Uwe an der Heiden, Dept. Mathematics and Theory of Complex Systems, University of

Witten/Herdecke, Witten• Andreas Deutsch, Center for High Performance Computing, Technical University of Dresden,

Dresden

Greece• Daphne Manoussaki, FORTH, Institute of Applied and Computational Mathematics, Foundation

for Research and Technology, Crete

Israel• Zvia Agur, Institute for Medical BioMathematics, Bene Ataroth

Poland• Miroslaw Lachowicz, Department of Mathematics, Computer Sciences and Mechanics, University

of Warsaw, Warsaw

Spain• Miguel Angel Herrero, Departamento de Matematica Aplicada, Facultad de Matematicas,

Universidad Complutense Madrid , Madrid

Sweden• Magnus Willander, Laboratory of Physical Electronics and Photonics, School of Microtechnology,

Gothenburg University and Chalmers University of Technology, Gothenburg

United Kingdom• Helen Byrne, Centre for Mathematical Medicine, School of Mathematical Sciences, University of

Nottingham, Nottingham• Mark Chaplain, The SIMBIOS Centre, Division of Mathematics, University of Dundee, Dundee


TOWARDS THE NEURONAL MACHINE

Proposal acronym NEURO EC contribution (€) 1.945.500Contract n° FP6-2003-NEST-B1-12788 Instrument NEST-ADVENTUREDuration (starting date) 3 years (01.05.2005) Participants 5

Abstract:

Artificial intelligence, computer vision and robotics are limited in their development and practical application because theyrequire highly parallel processing, but usually run on the existing computers which are serial machines i.e. with the wronghardware. In order to develop highly parallel machines many directions are being explored, like cellular siliconstructures, quantum computing, optical computing and biocomputing.Advances in the biocompatibility of materials and electronics have allowed neurons to be cultured directly on metal orsilicon substrates, so called Multi-Electrode Arrays (MEA), through which it is possible to stimulate and record Neuronalelectrical activity. Therefore, it is desirable to explore the possibility of using biological neurons as computing elements intasks commonly solved by conventional silicon devices. The aim of the “Neuro“ project is to make further advances in thedevelopment of a Neurocomputer, which in 5 or 10 years may become a commercially viable new computational device.This new device is based on arrays of living neurons and capable of massive parallel processing with a parallelism leveland a computational speed not achievable with the present silicon technology. The project is based on experimentalresults already obtained on small-scale devices, and will be based on the solution of three major problems whichNeurocomputers have to solve in order to become effective new computing devices: - 1 Neuronal (Wetware) Technology:it is necessary to have control of the wetware, i.e. the biological computing elements. Therefore it is necessary to selectand standandize the neurons composing the culture. – 2 Hardware development: It is also necessary to develop MEAwith a larger number of electrodes with appropriate software and hardware capability. - 3 Algorithmic Analysis andsoftware development: it is necessary to understand which computational problems of Artficial Intelligence, Robotics andComputer Science can be solved with Neurocomputers and which Wetware is the most appropriate for specificproblems. Therefore the present consortium brings together one of the best known European specialists in Neuronalstem cells, the leading European manufacturer of MEA and three scientists experienced in the use of MEAs who have astrong background in neuroscience, computer science and computational neuroscience. This combination of partnershas all the expertise required to successfully accomplish the project aims.

Web site: not yet (planned for 2007)

Participants:

Coordinator

Italy

Prof. Vincent Torre, Neurobiology Sector, Scuola Intern. Superiore di Studi Avanzati, Triestetel: +39 040 3756520 fax: +39 040 [email protected]

Germany• Karl-Heinz Boven, Multi Channel Systems MCS GmbH, Reutlingen, SME• Ad Aertsen, Dept. of Neurobiology and Biophysics, Albert-Ludwigs-University Freiburg

Italy• Angelo Vescovi, Dipartimento di Biotecnologie e Bioscienze (BtBs), Università degli Studi di

Milano-Bicocca (UNIMIB), Milan

United Kingdom• Hugh Robinson, Department of Physiology, University of Cambridge


SHORT-TERM IN VITRO ASSAYS FOR LONG-TERM TOXICITY

Proposal acronym PREDICTOMICS EC contribution (€) 2.259.754Contract n° LSHB-CT-2004-504761 Instrument STREPDuration (starting date) 3 years (01.09.04) Participants 13

Abstract:

The development of new pharmaceutical compounds will be more efficient if human relevant toxicology information earlyin the selection process is available. While acute toxicity can be reasonably detected during the early preclinical stagesof drug development, long-term toxicity is more difficult to predict, relying almost exclusively on animal experiments.Animal experimentation of this kind is expensive and time consuming, raises ethical issues and does not necessarilyrepresent a toxicological relevance to man. This project addresses the urgent need to develop in vitro based systemswhich are capable of predicting long term toxicity in humans. The major objectives of this project are:1) To develop advanced cell culture systems which as best possible represent the human liver and kidney in vivo. Thiswill be achieved using combined strategies namely: co-cultures of resident cell types, target cell transformation, stem celltechnology and new developments in organotypic cell culture (i.e. perfusion cultures and 3D cultures).2) To identify specific early mechanistic markers of toxin induced cell alterations by using integrated genomic, proteomicand cytomic analysis.3)To establish and prevalidate a screening platform (cell systems together with analysis tools) which is unambiguouslypredictive of toxin induced chronic renal and hepatic disease.This proposal is unique in it's mechanistic integration of the three levels of cellular dynamics (genome, proteome andcytome) together with advanced cell cultur technology to detect early events of cellular injury. Only with such anintegrated approach will in vitro techniques ever be applicable to predicting chronic toxicity in man. This project, ifsuccessful will (1) contribute to the replacement of animal testing in drug development, (2) increase the speed the cost ofbringing new pharmaceutical compounds to the patient and (3) increase our understanding of toxin induced chronic renaland hepatic disease.

Web site: http://www.predictomics.com

Participants:

Coordinator

Spain

Dr Dr José Castell Ripoll, Fundación Hospital "La Fe", Valenciatel: +34 96 1973 048 fax: +34 96 1973 [email protected]

Austria• Walter Pfaller, University of Innsbruck

Belgium• Vera Maria Rogiers, Vrije Universiteit Brussel• Philippe Vanparys, Janssen Pharmaceutica N.V., Beerse, IND• Bernward Garthoff, European Consensus Platform on 3R-Alternatives, Brussels

France• Patrick Maurel, Institut National de la Santé et de la Recherche Médicale, Montpellier

Germany• Gabriele Scholz, Bayer AG, Wuppertal, IND

Ireland• Michael P. Ryan, National University of Ireland, Dublin

Italy• Thomas Hartung, Joint Research Centre, Ispra

Netherlands• Mohammed Daha, Leiden University Medical Centre

Spain• Gorka Ochoa, Medplant Genetics S.L., Baracaldo, SME• Manzanares Ignacio, PharmaMar S.A. Sociedad Unipersonal, Colmenar Viejo Madrid, SME

Switzerland• Armin Wolf, Novartis Pharma AG, Basel, IND


DEVELOPMENT OF A NOVEL APPROACH IN HAZARD AND RISK ASSESSMENTOR REPRODUCTIVE TOXICITY BY A COMBINATION AND APPLICATION OF

IN VITRO, TISSUE AND SENSOR TECHNOLOGIES

Proposal acronym ReProTect EC contribution (€) 9.100.000Contract n° LSHB-CT-2004-503257 Instrument IPDuration (starting date) 5 Years (01.07.04) Participants 26

Abstract:

Validated alternative test methods are urgently required for safety toxicology of drugs, chemicals and cosmetics. Whilesome animal tests for topical toxicity have been successfully replaced one by one by alternative methods, systemictoxicities require new test strategies in order to achieve an adequate safety level of the consumer. In the project, ECVAM(the European Centre for the Validation of Alternative Methods) will support the management of developing a conceptualframework in the area of reproductive toxicity. The involvement of all stakeholders in the Project Board including theEuropean Consensus Platform on Alternatives (ECOPA), European regulators, OECD, and Industry guarantees anefficient problem solving approach. Reproductive toxicity offers the opportunities that: (i) a substantial number of animalsare currently required in in vivo assays; (ii) the reproductive system can be broken down into well-defined sub-elementscovering the reproductive cycle; (iii) a number of pioneering alternatives have already been developed; and (iv) the sameanimal experiments are carried out for drugs, chemicals and cosmetics. The project is composed of four elements, i.e.(a) technological development of in vitro and (b) sensor technologies (c) the strategical development of a conceptualframework (d) the dissemination and implementation activities The project will develop the concepts required to composetesting strategies via the continuous implementation of novel in vitro and in silico alternatives. Problems to be solvedinclude the development of substantial numbers of alternative test methods making use of advanced technologies. Thisapproach requires the dimensions of a transnational Integrated Project, involving some of the most prominentreproductive toxicity research groups in the EU, close monitoring by and input from the regulatory community andprofessional managerial steering. In return, it offers the realistic opportunity to achieve a substantial reduction of animalexperimentation.

Web site: http://ecvam.jrc.it

Participants:

Coordinator

Germany

Dr Michael Schwarz, Eberhards Karls Univ. Tübingen, Institute of Pharmacology and Toxicologytel: +49 7071 29 77398 fax: +49 7071 29 [email protected]

Austria• Alois Jungbauer, Institute of Applied Microbiology, Vienna

Belgium• Johan Smitz, Vrije Universiteit Brussel• Jean Mesens, Janssen Pharmaceutica NV, Beerse, IND• Rita Goergette Cortvrindt, EggCentris NV, Zellik, SME• Hilda Witters, Vlaamse Instelling voor Technologisch Onderzoek, Mol

Bulgaria• Mekenyan Ovanes, Bourgas University

Denmark• Elisabeth Ehlert Knudsen, University of Copenhagen

France• Anne Tilloi, Pfizer PGRD, Amboise, IND

Germany• Horst Spielmann, Zentralstelle zur Erfassung und Bewertung von Ersatz- und

Ergänzungsmethoden zum Tierversuch (ZEBET), Berlin• Alexius Freyberger, Bayer Healthcare AG, Wuppertal, IND• Andre Schrattenholz, ProteoSys AG, Mainz, SME• Hans Nau, School of Veterinary Medicine, Hannover• Corinna Hermann, Steinbeis Technology Transfer Center, Konstanz, SME

Italy• Giovanna Lazzari, Consorzio per l'Incremento Zootecnico srl, La Serra di San Miniato, SME• Alberto Mantovani, Istituto Superiore di Sanità, Rome• Andrea Galli, Istituto Sperimentale Italiano Lazzaro Spallanzani, Milano• Marcello Spanò, Ente Per Le Nuove Tecnologie l’Energia e l'Ambiente, Roma• Thomas Hartung, EU Joint Research Centre, Ispra

Netherlands• Axel Themmen, Erasmus MC, Rotterdam• Bart Van Der Burg, BioDetectionSystems BV, Amsterdam, SME• Aldert Piersma, National Institute for Public Health and the Environment, Bilthoven• Ine Waalkens-Berendsen, Netherlands Organization for Applied Scientific Research, Delft

Sweden• Lennart Dencker, Uppsala universitet

United Kingdom• Ilpo Tapani Huhtaniemi, Imperial College, London• Mark Timothy David Cronin, John Moores University, Liverpool


REDUCING ANIMAL EXPERIMENTATIONIN PRECLINICAL PREDICTIVE DRUG TESTING

BY HUMAN HEPATIC IN VITRO MODELS DERIVED FROM EMBRYONIC STEM CELLS

Proposal acronym VITROCELLOMICS EC contribution (€) 2.942.000Contract n° LSHB-CT-2005-018940 Instrument STREPDuration (starting date) 3 years (01.01.06) Participants 9

Abstract:

The objective of the proposal is to establish stable cell lines that reliably reflect human hepatic properties by thedevelopment of models derived from human embryonic stem cells (hESC). The aim is to deliver reliable in vitro modelsthat can be used by the pharmaceutical industry to replace experimental animals in investigations on human drugmetabolism, uptake and efflux properties of compounds in the drug discovery and development processes. In thepharmaceutical industry reliable in vitro cell models would replace current techniques and animal experimentation in theselection and optimisation of lead compounds and in documentation of a selected drug candidate before it enters clinicalphases. ? The means to accomplish the objective are in addition to hESC derived hepatocytes, (1) 3D-hepatic cellmethods, (2) micro-cultivation monitoring for in vitro screening, (3) genomic and metabolomic characterization, and (4) amulti-micro-bioreactors for high-throughput screening of drug candidates. Comparative studies with established in vitromodels will be carried out to validate the new models/methods. ? The outcome of the project is new pre-validation modelswhich will reduce the use of animal experimentation for prediction of human drug metabolism and disposition by 60-80%.In addition, the models will also increase safety and quality of compounds chosen as candidates in the different stages ofthe drug discovery and development process. Furthermore, it will strengthen the possibility for SMEs to market newpotential products for assays and in vitro screening. ? The clinical expertise in the project includes two renownedEuropean university hospitals, one SME founded by another European university hospital, and a larger pharmaceuticalcompany. The coordinator and several partners have a background from pharmaceutical industry which is paired withpartners very experienced in bioengineering.

Web site: http://www.vitrocellomics.org

Participants:

Coordinator

Sweden

Prof. Carl-Fredrik Mandenius, Institute of Technology, Linköping University, Linköpingtel: +46 13 288967 fax: +46 13 [email protected]

Belgium• Sandra Coecke, Institute for Health and Consumer Protection, Joint Research Center, Ispra (VA),

Bruxelles

Germany• Elmar Heinzle, Technische Biochemie, Universität des Saarlandes, Saarbrücken• Jörg Gerlach, Division of Experimental Surgery, Clinic for General, Visceral and Transplantation

Surgery, Charité University Medicine Berlin• Ruth Maria Maas, Pharmacelsus GmbH, Saarbrücken

Portugal• Manuel Carrondo, Animal Cell Technology Laboratory, Instituto de Biologia Experimental e

Technológica, Oeiras

Sweden• nger Johansson, Division of Molecular Toxicology, IMM, Karolinska Institutet, Karolinska Institutet,

Stockholm• Petter Björquist, Cellartis AB, Göteborg, SME• Tommy B. Andersson, AstraZeneca R&D Mölndal, DMPK and Bioanalytical Chemistry,

AstraZeneca AB, Mölndal, IND


REPAIRINGPreclinical and clinical studies for diseases and impairments

BETA CELL PROGRAMMING FOR TREATMENT OF DIABETES

Proposal acronym BETACELLTHERAPY EC contribution (€) 11.788.000Contract n° LSHM-CT-2005-512145 Instrument IPDuration (starting date) 5 Years (01.04.05) Participants 22

Abstract:

Diabetes is a frequent chronic disease that reduces quality of life and increases risks for life-threatening complications.Its onset in younger patients is caused by massive losses in insulin-producing beta cells. Regenerating a functional betacell mass is thus a major goal in biomedicine and in society. Beta cell grafts prepared from human pancreases can curethe disease but development of this form of beta cell therapy is hindered by shortage in donor organs. Our consortiumwith leading teams in molecular, developmental and functional biology has worked out an integrated program to generateinsulin-producing beta cells in therapeutic quantities and established interactions to translate knowledge to associatedbioindustry and multicenter clinical trials, as well as to society. Nature's biologic program to develop and preserve afunctional beta cell mass throughout life is taken as platform for directing strategies towards laboratory production of atherapeutic beta cell mass. Beta cells will be derived from embryonic stem cells and from transdifferentiating liver,intestinal and pancreatic exocrine cells. Functional genomics will be used to compare phenotypes of beta cells from newsources with those isolated from the pancreas. This analysis will direct further research and judge on the start ofpreclinical testing. It will also generate new tools and quality control criteria that will allow standardization of ongoing trialsand adjustments in graft biology to increase its long-term survival and function in patients. The consortium considers itsplan realistic in its perspective to help develop a cure for diabetes by (re)programming cells for beta cell therapy.

Web site: http://www.betacelltherapy.org

Participants:

Coordinator

Belgium

Dr. Daniel Pipeleers, Dr. Harry Heimberg, Prof. Luc Bouwens, Vrije Universiteit Brusseltel: +32 2 477 45 41 fax: +32 2 477 45 [email protected], [email protected], [email protected]

Belgium• Frederic Lemaigre, Universite catholique de Louvain• Bernard Peers, University of Liege• Christel Hendrieckx, JDRF Center for Beta Cell Therapy in Europe, Brussels• Zhidong Ling, Academic Hospital VUB, Brussels• Andreas Jahraus, Beta-Cell NV, Zellik, SME• Luc Marina Francois Schoonjans, Thromb-X NV, Louvain, SME

Denmark• Jens H. Nielsen, University of Copenhagen• Finn Cilius Nielsen, Hospital Rigshospitalet, University of Copenhagen• Ole D. Madsen & Palle Serup, Novo Nordisk A/S, Gentofte, IND• Thomas Rolf Mandrup-Poulsen, Steno Diabetes Center, Gentofte

France• Philippe Ravassard, Centre National de la Recherche Scientifique, Paris• Raphael Scharfmann, Institut National de la Sante et de la Recherche Medicale, Paris

Israel• Shimon Efrat, Tel Aviv University

Spain• Fatima Bosch, Universitat Autonoma de Barcelona, Bellaterra (Cerdanyola del Valles)• Jorge Ferrer, Hospital Clinic Provincial de Barcelona, Barcelona

Sweden• Henrik Semb, Lund University• Johan Hyllner, Cell Therapeutics Scandinavia AB, Gothenburg, SME

Switzerland• Pedro Luis Herrera, Faculte de Medecine, Universite de Geneve• Anne Graphin-Botton, Swiss Institute for Experimental Cancer Research, Epalinges/Lausanne

United Kingdom• Jonathan Michael Wyndham Slack, University of Bath• Dominic John Withers, University College London


SOFT TISSUE ENGINEERING FOR CONGENITAL BIRTH DEFECTS IN CHILDREN:NEW TREATMENT MODALITIES FOR SPINA BIFIDA,

UROGENITAL AND ABDOMINAL WALL DEFECTS

Proposal acronym EuroSTEC EC contribution (€) 7.828.500Contract n° LSHB-CT-2006-037409 Instrument IPDuration (starting date) 5 years (01.01.07) Participants 14

Abstract:

The aim of this project is to use modern tissue engineering approaches to treat children with structural disorders presentat birth, such as spina bifida, urogenital defects, gastroschisis, diaphragmatic hernia and esophageal atresia. The projectstrives to take a translational route through in vitro and animal experiments to early clinical trials.Tailor-made 'smart' biomatrices (scaffolds) will be prepared using natural scaffold molecules (collagen, elastin) and/ormen-made polymers (poly lactic/glycolic acid), and will be substituted with regulatory molecules such as growth factorsand glycosaminoglycans.A variety of cells, including stem cells, fibroblasts, muscle cells and urothelial/epithelial cells will be cultured in vitro andseeded into biomatrices. Biomatrices thus prepared, will be implanted using novel animal models for major congenitalbirth defects, and evaluated for their capacity to regenerate the correct tissues. Biomatrices will degrade in time and bereplaced by the bodies own tissues thus assuring compliance with growth which is especially important in young children.Prenatal and postnatal reconstructive procedures will improve the final outcome of reconstructive surgery. Clinical trialsfor diaphragmatic hernias will form the start of the patient registry and protocol development for future clinical studies.Ethical and regulatory issues will be fully addressed before final clinical application, and parents and children will have tobe able to understand these new treatment options. A dialogue with society, including patient's associations, will besought. Demonstration activities will be undertaken to increase the awareness of new treatment modalities based ontissue-engineering. Finally, surgeons will be trained to use the new operation techniques.The project combines European leaders in the field of biomatrices, cell culture, animal models, surgery, and ethical andregulatory issues.

Web site: not yet

Participants:

Coordinator

Netherlands

Dr. Wouter Feitz, Department of Urology, Stichting Katholieke Universiteit, Radboud UniversityNijmegen Medical Centre, Nijmegentel: +31-24-3613735 fax: [email protected]

Austria• Amulya Saxena, Department of Paediatric Surgery, Medizinische Universitaet Graz (Medical

University of Graz), Graz

Belgium• Jan Deprest, Department of Obstetrics and Gynaecology, Katholieke Universiteit Leuven, Leuven

France• Benjamin Herbage, Symatese Biomateriaux, Chaponost, IND

Germany• Ingo Heschel, Research, Matricel GmbH, Herzogenrath, SME• Gerard Barki, KARL STORZ GmbH & Co.KG, Tuttlingen, IND

Netherlands• Paul Van den Berg, Department of Obstetrics and Gynaecology, University Medical Centre

Groningen, Groningen• Wim Witjes, Clinical Research, CuraTrial SMO & Research BV, Arnhem• Noes De Vries, European Medical Contract Manufacturing, Nijmegen, SME

Spain• Eduard Gratacos, Department of Obstetrics, Fetal Medicine and Therapy Research Group,

Hospital Clinic, Institut d'Investigacions Biomediques August Pi I Sunyer, Barcelona

Sweden• Jons Hilborn, Department of Polymer Chemistry, Materials Chemistry, Uppsala University,

Uppsala

Switzerland• Peter Frey, Department of Pediatric Urology and Surgery, CHUV, and Integrative Bioscience

Institute EPFL, Centre Hospitalier Universitaire Vaudois, Lausanne• Andreas Zisch, Obstetrics, University Hospital Zurich, University Zurich, Zurich

United Kingdom• Kypros Nicolaides, Harris Birthright, Fetal Medicine Unit, King's College Hospital, The Fetal

Medicine Foundation, London


CLINICAL EXPERIENCE WITH BONE MARROW CELLSAND MYOBLASTS TRANSPLANTATION FOR MYOCARDIAL REPAIR

Proposal acronym MYOCARDIAL REPAIR EC contribution (€) 400.000Contract n° LSSM-CT-2004-511992 Instrument SSADuration (starting date) 30 Months (01.01.05) Participants 9

Abstract:

Heart failure caused by the ischaemic heart disease is one of the most common causes of morbidity an mortality acrossEurope, especially high among elderly people, but the post-infarction myocardial injury is also major cause of disability inyounger survivors from myocardial infarction. The proposed project is dedicated to stimulate "state-of-the-art" researchon the clinical applications of autologous stem cells, including bone marrow derived stem cells as well as myoblasts, tothe regeneration of heart muscle in irreversibly damaged post-infarction regions. The consortium includes mostexperienced European clinical researchers in the field, which already had accomplished the phase I clinical trials inparticipating centres. The researchers from participating centres have agreed to coordinate their future clinical trials onstem cell transplantation for myocardial regeneration in patients with postinfarction heart failure, as a result of theproposed project. This will include analysis of polled clinical data obtained in participating centres, reciprocal exchange ofinformation on cell culture and cell preparation for transplantation. This will also include standardization of clinicalprotocols aiming at evaluation of the clinical efficacy of myocardial replacement therapy as well as hand-on training ofdifferent techniques of cell delivery, including percutaneous cell transplantations, in particular trans-coronary arteriesbone marrow stem cell delivery protocols as well as trans-ventricular and trans-cardiac-veins myoblast injectiontechniques. As a result of further integration of the consortium, it is expected to stimulate formation of a common futurephase III studies at international level, especially with an option of submitting future Integrated Project application withinthe 6th Framework Programme.

Web site: none

Participants:

Coordinator

Poland

Prof. Tomasz Siminiak, University School of Medical Sciences, Department of Cardiology, DistrictHospital, Poznantel: +48 618 212 422 fax: +48 618 212 [email protected]

Czech Republic• Peter Widimsky, Charles University Prague, Cardiocenter Vinohrady, III Cardiology Clinic, Prague

France• Phillipe Menasche, Hopital Europeen Georges Pompidou, Dept. of Cardiology, Paris• Jean Ponsonnaille, University Hospital, Department of Cardiology, Region of Auvergne and

University of Auvergne Medical Center, Clermont Ferrand

Germany• Gustav Steinhoff, University of Rostock, FGKO, Klinik und Poliklinik fur Herzchirurgie, Rostock

Lithuania• Vytautas Jonas Sirvydis, Vilnius University, Faculty of Medicine, Heart Surgery, Centre of Heart

Clinic, Vilnius

Netherlands• Patrick Serruys, Erasmus University Rotterdam, Thoraxcenter, Interventional Cardiology,

Rotterdam

Poland• Maciej Kurpisz, Polish Academy of Sciences, Institute of Human Genetics, Department of

Reproductive Biology and Stem Cells, Poznan

Spain• Francisco Fernandez-Aviles, Univ. Valladollid, Inst. de Ciencias Del Corazon, ICICOR, Valladolid


FROM STEM CELL TECHNOLOGY TO FUNCTIONAL RESTORATIONAFTER SPINAL CORD INJURY

Proposal acronym RESCUE EC contribution (€) 2.700.000Contract n° LSHB-CT-2005-518233 Instrument STREPDuration (starting date) 3 years (01.12.2005) Participants 9

Abstract:

Spinal cord injuries (SCI) have long been regarded as intractable, largely due to the alleged inability of the mammalianCMS to regenerate. However, over the last two decades, technological advances combined with the understanding of thepathophysiology of SCI have progressed to the point where it is now conceivable to develop therapeutic interventionstrategies aimed at reconstructing the neuronal circuitry damaged by the lesion. One of the most powerful tools for thisobjective is based on stem cells, which can be used in three different ways to achieve this goal: 1) to bring permissivemolecules and/or trophic agents at the level of the lesion to enhance the regenerative capacity of severed axons; 2) to useas replacement cells, grafted locally to stimulate specific circuits such as the central pattern generator (CPG); 3) toenhance the reparative potential of intrinsic stem cells. Most of the program will concentrate on human adult stem cellsgenerated from bone marrow and adult CNS (including the spinal cord), but we will also consider foetal stem cells andestablished cell lines. Rodent cells will also be used as a model. This program will be achieved in three steps: Harvestingof adult and/or foetal stem cells (neural and non-neural), to be used directly or after transformation through geneticengineering. Grafting in the injured cord. Monitoring of the grafted cells with in vivo imaging, and assessing their effectsusing functional studies. It will require several technical prerequisites including standardisation for the harvesting ofhuman stem cells, for the spinal cord lesion models, for the transplantation paradigms and for the functional studies. Thefinal objective of the present project is the translation of experimental studies to clinical practice through the elaboration ofa series of therapeutic tools to be used in a wide variety of clinical paradigms of SCI.

Web site: not yet

Participants:

Coordinator

France

Prof. Alain Privat, INM, Institut National de la Santé et de la Recherche Médicale, Montpelliertel: +33 499636006 fax: +33 [email protected]

Belgium• Jean Schoenen, University of Liège, Liège

Czech Republic• Eva Sykova, Institute of Experimental Medicine ASCR, Institute of Experimental Medicine,

Academy of Sciences of the Czech Republic, Prague

France• Jacques Mallet, Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus

Neurodégénératifs, Centre National de la Recherche Scientifique, Paris• Manuel Gaviria, Neuréva Inc., Montpellier, SME• Aude Sirven, Inserm transfert, Paris

Germany• Gary Anthony Brook, Rheinisch-Westfälische Technische Hochschule for the faculty of medicine,

University Hospital Aachen, Aachen

Spain• Minerva Gimenez y Ribotta, Instituto de Neurociencias, Unit Neurobiology of Development, Lab.

spinal cord pathology, Spanish National council for scientific research, Alicante

United Kingdom• Jack Price, Department of Neuroscience, King's College London, London


APPLICATION AND PROCESS OPTIMIZATION OF HUMAN STEM CELLSFOR MYOCARDIUM REPAIR

Proposal acronym SC&CR EC contribution (€) 1.954.200Contract n° LSHB-CT-2003-502988 Instrument STREPDuration (starting date) 3 years (01.02.04) Participants 10

Abstract:

Myocardial infarction (Ml) is an irreversible injury where sudden interruption of blood flow caused by the occlusion of anartery leads quickly to cardiac myocytes death, loss of tissue and scar formation. Since the self-renewal ability of adultcardiac myocytes is limited, the development of strategies to regenerate damaged myocardium and improve its functionrepresents a major challenge in the treatment of cardiac diseases. Recent evidences have suggested that multipotentsomatic stem cells can become reprogrammed in new tissue-specific stem cell niches. However, despite the growingnumber of observations reporting "trans-differentiation" of adult tissue-derived stem cells, there are no conclusiveevidences on the mechanism(s) underlying changes in stem cell fate and sufficient information on the therapeuticpotential of these cells. In this proposal we aim to provide a contribution on validation of the use of adult tissue derivedstem cells for myocardial repair by:1) identifying the most suitable adult stem cell type(s) to be used to promote myocardial repair/regeneration;2) unraveling the combination of stimuli that might drive differentiation of stem cells toward a cardiac myocyte lineage;3) define genes and factors driving stem cell differentiation into cardiac lineage and set-up safe and effective vectors andprotocols to induce cardiac myocyte differentiation pathway(s) by gene transfer;4) assessing the functional properties of stem cell-derived cardiac myocytes;5) unraveling the action of factors that might be involved in recruitment and homing of endogenous stem cell inmyocardium;6) evaluating the mid- and long-term effects of stem cell administration by clinical trials of autologous hematopoietic stemcell administration in patients suffering ischemic heart disease.

Web site: http://www.sc-cr.org

Participants:

Coordinator

Italy

Dr. Maurizio Capogrossi Colognesi, Provincia Italiana della Congregazione dei Figlidell'Immacolata Concezione - Istituto Dermopatico dell'Immacolata, Rometel: +39 06 6646 2433 fax: +39 06 6646 [email protected]

Germany• Anna Wobus, Institute of Plant Genetics and Crop Plant Research, Gatersleben• Carsten Werner, Institut für Polymerforschung Dresden e V, Dept. Biokompatible Materialien• Michael Hallek, Gene Center, Ludwigs-Maximilians-University of Munich

Italy• Maurizio Pesce, Centro Cardiologico Monzino, Milan• Antonio Zaza, Università degli Studi Milano-Bicocca• Nadia Rosenthal, European Molecular Biology Laboratory, Monterotondo Scalo• Luigi Cavenaghi, Areta International, Milan, SME

Netherlands• Jacques De Bakker, Interuniversity Cardiology Institute of the Netherlands, Utrecht

Poland• Aldona Dembinska-Kec, The Jagiellonian University, Medical College, Krakow


TOWARDS A STEM CELL THERAPY FOR STROKE

Proposal acronym STEMSTROKE EC contribution (€) 2.475.508Contract n° LSHB-CT-2006-037187 Instrument STREPDuration (starting date) 3 years (01.01.07) Participants 6

Abstract:

Stroke is a major cause of long-term disability in humans, but effective treatments are lacking. The StemStrokeconsortium comprises 5 highly qualified academic research teams and one SME which, together with excellent cliniciansin the stroke field, will perform innovative research leading to the first preclinical protocol for application of stem celltherapy in stroke patients. Human neural stem cell (NSC) lines will be isolated from the foetal and adult brain, and fromembryonic stem cells. Cellular and molecular mechanisms regulating the proliferation, migration, survival, anddifferentiation of the NSC lines after transplantation into the stroke-damaged rodent brain will be determined. In parallel,StemStroke will unravel mechanisms regulating self-repair after stroke through formation of new neurons from the adultbrain's own NSCs. The StemStroke will explore the morphological and functional integration of grafted and endogenouslygenerated NSCs and their progeny in the stroke-damaged brain, and develop new in vivo imaging and behavioural tests,relevant for the human situation, for assessment of stem cell function and recovery of sensory, motor and cognitivedeficits. Finally, StemStroke will optimize transplantation- and endogenous neurogenesis-based strategies and create animportant preclinical protocol which can be rapidly translated into human trials.The teams contain top-level expertise in animal models of stroke and MRI-based in vivo imaging, stem cell, molecular,and cellular biology, molecular genetics, animal behaviour and psychology, translational research, and clinical celltherapy. Through the participating SME, commercial exploitation of the knowledge emerging from the project is ensured.The complementarity of expertise within the consortium, together with the intellectual and technological resourcesavailable from each partner, will ensure efficient and high-quality performance and feasibility of achieving its ambitiousS&T goals.

Web site: not yet

Participants:

Coordinator

Sweden

Prof. Zaal Kokaia, Clinical Neuroscience, Faculty of Medicine, Stem Cell Center UniversityHospital, Lund University, Lundtel: +46 462220276 fax: +46 [email protected]

Germany• Mathias Hoehn, In-vivo-NMR-Laboratory, Max-Planck-Institut für neurologische Forschung, Köln• Liliana Minichiello, EMBL-Mouse Biology Unit, EMBL-Monterotondo, European Molecular Biology

Laboratory (Monterotondo-Rome), Heidelberg

Sweden• Lilian Wikström, NeuroNova AB, Stockholm, SME

United Kingdom• Austin Smith, Institute For Stem Cell Biology, The Chancellor, Master, and Scholars of the

University of Cambridge, Cambridge• Stephen Dunnett, School of Biosciences, Cardif University, Cardiff


MULTIPOTENT ADULT PROGENITOR CELLS TO TREAT STROKE

Proposal acronym STROKEMAP EC contribution (€) 2.400.000Contract n° LSHB-CT-2006-037186 Instrument STREPDuration (starting date) 3 years (01.10.06) Participants 8

Abstract:

Successful therapy for stroke will be achieved using cells that can limit ischemic injury and differentiate into the multiplecell types needed for restoring blood flow and neural circuits, and would be available for therapy 'off the shelf¿. AsMultipotent Adult Progenitor Cells (MAPCs) differentiate into vascular and neural cells, and reconstitute damaged tissuesin vivo, we hypothesize that MAPCs is an ideal allogeneic cell product to treat stroke.In WP1, WP2 and WP3, we will develop approaches to generate committed vascular cells and neuroprogenitors, andidentify key molecular events that guide differentiation.WPs 4-7 will rigorously evaluate the pre-clinical efficacy of allogeneic MAPCs or their progeny in stroke. This will includedevelopment of noninvasive imaging techniques to follow the fate of grafted cells and evaluate their impact on CNSfunction (WP4). We will compare the efficacy of MAPCs with that of till now ¿gold-standard¿ stem cell populations instroke, and determine mechanisms underlying observed effects (WP5). We will examine the immunogenicity of MAPCsand their differentiated progeny in vitro (WP6) and in vivo using mice with a 'human immune system' (WP7).Studies in WP9 will develop clinical grade culture systems to generate human MAPCs and, if needed, lineage committedprogeny. Studies in WP8 will develop a framework in which to develop clinical grade stem cell products in an ethicallyresponsible manner. Specific attention to the management of the project. The management, exploitation anddissemination of the project will be ensured through WP10.These studies will lay the foundation for clinical trials of MAPCs in stroke in Europe in subsequent years. The highlyinnovative methods, tools and technologies that will be developed will not only be applicable in the area of stem cell basedtherapies for stroke, but may significantly advance use of human stem cells in regenerative medicine.

Web site: not yet

Participants:

Coordinator

Belgium

Prof. Catherine Verfaillie, Department Oncology - Hematology Transplantation, KatholiekeUniversiteit Leuven, Leuven, Leuven, BE, BE, Belgium, N, HE, PNP, +32 16 34 68 95, +32 16 34,[email protected]: +31 71 52 66 639 fax: +31 71 52 48 [email protected]

Belgium• Peter Carmeliet, Center for Transgene Technology and Gene Therapy, Vlaams Interuniversitair

Instituut voor Biotechnologie, Leuven• Gil Van Bokkelen, ReGenesys, Brussels, SME

France• Jean-Marc Idee, Research Department, Guerbet, Roissy Charles de Gaulle, IND

Spain• Felipe Prosper Cardoso, University Clinic of Navarra - Dept. of Hematology, University of Navarra,

Pamplona• Jose Manuel Garcia Verdugo, Dept. Neurobiologia Comparada Instituto Cavanilles, Universitat de

València. Estudi General, Paterna

Sweden• Ernest Arenas, Dept. of Medical Biochemistry and Biophysics, Divsion of Molecular Neurobiology,

Karolinska Institutet, Stockholm

Switzerland• Markus G. Manz, Institute For Research in Biomedicine, Institute for Research in Biomedicine,

Bellinzona


EX VIVO GENE THERAPY FOR RECESSIVE DYSTROPHIC EPIDERMOLYSISBULLOSA : PRE-CLINICAL AND CLINICAL STUDIES

Proposal acronym THERAPEUSKIN EC contribution (€) 1.523.000Contract n° LSHB-CT-2005-511974 Instrument STREPDuration (starting date) 3 years (01.07.05) Participants 9

Abstract:

We aim to develop ex vivo gene therapy of recessive dystrophic epidermolysis bullosa (RDEB, #OMIM 226600,*120120). RDEB is caused by loss of function mutations in the collagen VII gene (COL7A1) encoding anchoring fibrils. Itis one of the most severe genodermatoses in children and adults. The patients suffer from skin blistering since birth, andfrom severe local and systemic complications resulting in poor prognosis. We lack a specific treatment for RDEB, but exvivo gene transfer to epidermal stem cells shows therapeutic potential. We and others have shown in vitro correction ofprimary RDEB keratinocytes by retroviral and lentivirat COL7A1 cDNA vectors Reports of leukemia caused by retroviralinsertional mutagenesis in gene therapy of X-SCID steered us toward safer, 'Self Inactivating (SIN)' vectors. In Step I ofthis project, we will design safe SIN retroviral and lentiviral COL7A1 vectors. Different promoters and viral envelopeproteins will be tested for efficient gene delivery and expression in cultured primary keratinocytes and fibroblasts. We willstudy the proliferate capacity of transduced cells, assess long-term expression of recombinant collagen VII, and analyseproviral integration sites for deleterious effects. We will analyse synthesis, folding and secretion of recombinant collagenVII, and its ability to form anchoring fibres in a skin equivalent model and in skin grafts on mice. Vectors will beconstructed and produced with full traceability to Good Laboratory Practice (GLP) standards. In Step II, cell clonesproducing the highest titres of the selected SIN retroviral or lentiviral vector (mini-cell bank} will be expanded, evaluated,and a unique GMP master cell bank (MCB) will be established This MCB will be tested for safety, to be used in theproduction of clinical grade viral particles. Step III will be a pilot clinical trial (Phase I/II) of genetically correctedautologous skin grafts in selected patients. This project, which combines the complementary expertise of severalinternational groups, will serve as proof of principle for the treatment of RDEB, and as a model for the treatment ofsevere dermatological genetic disorders by ex vivo gene therapy.

Web site: http://www.debra-international.org/researche2.htm

Participants:

Coordinator

France

Prof. Alain Hovnanian, Institut National de la Sante et de la Recherche Medicale, Toulousetel: +33 5 61 77 90 79 fax: +33 5 62 74 83 [email protected]

France• Christine Bodemer, Centre Hospitalo-Univ. Necker Enfants Malades (Assistance Publique), Paris• Olivier Danos, Genethon, Evry• Jonathan Dando, INSERM Transfert SA, Paris

Germany• Luis Moroder, Max Planck Society for the Advancement of Sciences, represented by MPI of

Biochemistry, Martinsried

Switzerland• Yann Barrandon, Ecole Polytechnique Federale de Lausanne

United Kingdom• Irene May Leigh, Queen Mary & Westfield College, University of London• John Alexander McGrath, King’s College London, University of London• John Richard William Dart, DEBRA Europe, Crowthorne


GENE TRANSFER IN SKIN EQUIVALENTS AND STEM CELLS:NOVEL STRATEGIES FOR CHRONIC ULCER REPAIR AND TISSUE REGENERATION

Proposal acronym Ulcer Therapy EC contribution (€) 2.392.000Contract n° LSHB-CT-2005-512102 Instrument STREPDuration (starting date) 3 years (01.08.05) Participants 8

Abstract:

Chronic ulcers and defective tissue repair represent a major health problem. Conventional therapeutic approaches are notsufficient to guarantee an adequate healing in chronic ulcers and recurrence is frequent. Among non conventionaltreatments, short protein half-life and inefficient delivery to target cells have been identified as main limitations of thetopical application of recombinant growth factors. Similarly, the therapeutic effect of skin equivalent grafting was limited, inparticular due to impaired production of granulation tissue by the host. The present project relays on the development andvalidation of novel therapeutic strategies for tissue regeneration, based on the use of genetically modified stem cells andskin equivalents. The plan structure starts with a multidisciplinary research approach aimed at characterising the role andmechanism of action of potentially therapeutic proteins. In parallel, a wide analysis will be conducted to exploit the mostsuitable adeno and adeno-associated viral vectors for gene transfer into selected cell types. The research will be thentranslated towards in vivo application of genetically modified stem cells and skin equivalents, as delivery systems oftherapeutic proteins. The pathology chosen to validate these innovative therapeutic strategies is the impaired woundhealing, due to diabetes. The potential therapeutic effect of ex-vivo engineered skin equivalents and bone marrow-derivedstem cells will be therefore tested at first on diabetic animals, or other animal models of impaired wound healing. A PhaseI clinical trial of diabetic chronic ulcers, with autologous skin equivalents ex-vivo engineered to over-express nerve growthfactor as a therapeutic protein, will be then accomplished.

Web site: not yet

Participants:

Coordinator

Italy

Prof. Jürgen Hescheler, Universität Kölntel: +49 221 478 737 3 fax: +49 221 478 383 [email protected]

Germany• Michael Hallek, Gene Center, Inst. for Biochemistry of the Ludwigs-Maximilians Univ. of Munich• Sabine Eming, Depart. of Dermatology, University of Cologne

Italy• Maurizio Pesce, Centro Cardiologico Monzino - IRCCS, Milan• Nadia Rosenthal, European Molecular Biology Laboratory, Monterotondo Scalo (RM)• Elena Dellambra, IDI FARMACEUTICI SpA, Pomezia (RM), SME

Spain• Jose Luis Jorcano Noval, Centro de investigaciones energeticas medioambientales y

tecnologicas, Madrid

Switzerland• Sabine Werner, Swiss Federal Institute of Technology, Zurich


TREATING

Improvement of standard hematopoietic stem cell transplantation

41

THE DEVELOPMENT OF IMMUNOTHERAPEUTIC STRATEGIESTO TREAT HAEMATOLOGICAL AND NEOPLASTIC DISEASES

ON THE BASIS OF OPTIMISED ALLOGENEIC STEM CELL TRANSPLANTATION

Proposal acronym ALLOSTEM EC contribution (€) 8.000.000Contract n° LSHB-CT-2004-503319 Instrument IPDuration (starting date) 3.5 years (01.05.04) Participants 27

Abstract:

Haematological disease, either malignant or otherwise, carries a significant burden of morbidity and mortality. Recentadvances in mapping and sequencing of the human genome make possible an approach to the treatment of thesediseases which exploits the genetic differences between individuals to produce targets through which the immune systemcan eliminate the diseased cells. In practice this process of immunotherapy involves an allogeneic haematopoïetic stemcell transplant, with subsequent delivery of specific immune effector cells expanded from the donor. The AlloStem projectbrings together clinical and research groups from across the EU who individually are amongst the world leaders in thefield of immunotherapy to coordinate and complement their efforts into a unified and directed program. We will developnew protocols for the treatment of patients with haematological disease and for the effective delivery of immunogenomics-based therapies. The end results of the project will be both an improvement in the health care for EU citizens and thedevelopment of new genome-based pharmaceuticals that can be exploited worldwide.

Web site: http://www.allostem.org

Participants:

Coordinator

United Kingdom

Prof. Alejandro Madrigal, The Anthony Nolan Trust, Londontel: +44 207 28 48 315 fax: +44 207 28 48 [email protected]

Argentina• Javier Bordone, ITMO-Fundación Mainetti, Gonnet

Brazil• Ricardo Pasquini, Hospital de Clinicas, Universidade Federal do Paraná, Curitiba

Czech Republic• Jirina Bartunkova, Charles University Prague

France Dominique Charron, HLA et MEDECINE , Paris François Romagne, Innate Pharma SAS, Marseille, SME Eric Vivier, Centre National de la Recherche Scientifique, Marseille Laurence Zitvogel, Institut Gustave Roussy, Villejuif

Germany Hermann Einsele, Eberhard Karls Universität Tübingen Mario Assenmacher, Miltenyi Biotec GmbH, Bergish-Gladbach, IND Hans-Georg Rammensee, Eberhard-Karls-Universitaet Tuebingen Dolores J. Schendel, GSF Nat. Research Center for the Environment and Health, Neuherberg

Israel Yair Reisner, Weizmann Institute of Science, Rehovot

Italy Head Locatelli, IRCCS Policlinico San Matteo, Pavia Alessandro Moretta, University of Genova Lorenzo Moretta, Istituto Giannina Gaslini, Genova Andrea Velardi, University of Perugia

Netherlands Johan Herman Frederik Falkenburg, Leiden University Medical Center

Poland• Andrzej Lange, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of

Sciences, Wroclaw

RussianFederation

• Leonid Alexeev, State Research Center, Moscow

Spain Manuel-Nicolas Fernandez, Universidad Autonoma de Madrid Joan Garcia, Centro de Transfusio Banc de Teixits, Barcelona

Sweden• Pavel Pisa, Karolinska institutet, Stockholm

United Kingdom Alejandro Madrigal, AlloStem, London, SME Peter Michael Maguire, Dynal Biotech Ltd , Bromborough, SME Nikolai Schwabe, PROIMMUNE Limited, Oxford, SME Robert Charles Rees, Nottingham Trent University


FACILITATING INTERNATIONAL PROSPECTIVE CLINICAL TRIALSIN STEM CELL TRANSPLANTATION

Proposal acronym CLINT EC contribution (€) 500.000Contract n° LSSB-CT-2007-037662 Instrument SSADuration (starting date) 2 years (01.04.07) Participants 4

Abstract:

Stem cell transplantation (SCT) is the treatment of choice for many blood diseases. Within healthcare provision, SCT isone of the most costly and one of the most risky procedures for patients with transplant related mortalities of up to 50%.SCT remains on the cutting edge of translational medicine and recently there have been many changes in the way intransplant methodology such as the introduction of new drugs and technologies. These innovations have the potential toimprove patient outcome but also to increase the cost considerably. At the same time there are many new developmentswith respect to targeted drug therapies and supportive care in these diseases which may replace or delay transplant forsome patients. These new therapies are also expensive and require urgent evaluation. It is essential that they and SCTare used wisely and economically. The SCT community is always prepared to critically evaluate the role of transplant, asis exemplified by the transmission of outcome data from individual centres to a central database held by the EuropeanTransplant Group (EBMT) for further analysis and reporting. SCT physicians have also been enthusiastic exponents ofclinical trials and are ready to test new hypotheses and to compare SCT with other treatments. Their ability to do this hasbeen severely curtailed by the recent requirements imposed by the EU Directive on Clinical Trials. Although introducedwith laudable intentions the effect of the Directive has been to increase the resources and therefore the expense of clinicaltrials whilst at the same time national differences in interpretation of the new legislation has rendered international studiesvery difficult. The objective of this SSA is to support the EBMT to further develop the infrastructure necessary to performacademically initiated international prospective studies in SCT throughout Europe. This will hasten the evaluation of newtreatment strategies and improve the outcome for European citizens.

Web site: not yet

Participants:

Coordinator

United Kingdom

Prof. Jane Apperley, Department of Haematology, Division of Investigative Sciences, ImperialCollege of Science, Medicine and Technology, Londontel: +44 20 8383 3237 fax: +44 20 8742 9335 [email protected]

Netherlands• Harry Schouten, University Hospital Maastricht, Dept. Internal Med. Hematology / Oncology,

European Group for Blood and Marrow Transplantation, Maastricht

United Kingdom• Doris Schroeder, Centre for Professional Ethics, University of Central Lancashire, Preston

United States• Mary Horowitz, CIBMTR, Medical College of Wisconsin Center for International Blood and Marrow

Transplant Research, Milwaukee


STRENGTHEN AND DEVELOP SCIENTIFIC AND TECHNOLOGICAL EXCELLENCE INRESEARCH AND THERAPY OF LEUKEMIA (CML, AML, MDS, CLL, ADULT ALL) BYCOOPERATION AND INTEGRATION OF THE LEADING NATIONAL LEUKEMIA NET

Proposal acronym EUROPEAN LEUKEMIANET EC contribution (€) 6.000.000Contract n° LSHC-CT-2004-503216 Instrument NoEDuration (starting date) 5 years (01.09.04) Participants 116

Abstract:

Leukemias are a challenge to society and a cost factor because of their frequency in all age groups. They also serve asa model for a variety of diseases and possess exemplary relevance for basic research and patient care. Leukemiaresearch and therapy have achieved high standards and even a leading position in several European countries withregard to clinical trials, standardisation of diagnostics and molecular studies of signal transduction and gene expression.A true European world leadership, however, has not been accomplished yet due to national fragmentation of leukemiatrial groups, diagnostic approaches and treatment research activities and a need for central information andcommunication structures.The objective is to integrate the leading leukemia trial groups (CML, AML, ALL, CLL, MDS, CMPD), their interdisciplinarypartners (diagnostics, treatment research, registry, guidelines), industry and SMEs across Europe form a European co-operative network for advancements in leukemia-related research and health care. Integration will be supported bycentral information, communication, education and management structures. The main goals are to intensify target anddrug discovery, to shorten the time period to clinical translation, to apply advanced genomics, telematics andbiotechnology to therapeutic progress and to promote translational research relevant also for solid cancers by largeclinical trials. Furthermore, metanalyses of specific subaspects,elaboration of prognostic scores, recognition of genderspecific differences, creation of uniform data sets for trials and registration, introduction of standards for diagnostics andtreatment procedures and development of evidence based guidelines will be promoted throughout Europe. The proposednetwork will have the expertise and critical mass for European added value and world leadership. It will structureEuropean research durably, spread European scientific excellence in the field of leukemias and can start immediately.

Web site: http://www.leukemia-net.org

Participants:

Coordinator

Germany

Prof. Rudiger Hehlmann, Ruprecht-Karls-Universität Heidelbergtel: +49 621 383 411 5 fax: +49 621 383 420 [email protected]

Austria• Günther Gell, Institut f. Med. Informatik, Statistik u. Dokumentation, Universitat Graz• Josef Thaler, Allg. ö. Krankenhaus der Barmherzigen Schwestern vom heiligen Kreuz, Wels• Christa Fonatsch, Medizinische Universität Wien• Oskar Haas, Children's Cancer Research Institute, Vienna• Heinz Zwierzina, Universität Innsbruck

Belgium• Anne Hagemeijer, Katholieke Universiteit Leuven• Philippe Martiat, Institut Jules Bordet, Université libre de Bruxelles

Croatia• Labar Boris, University Hospital Center, Zagreb

Czech Republic• Jiri Mayer, The Brno Faculty Hospital

Denmark• Peter Hokland, Aarhus University Hospital• Christian Geisler, HS Rigshospitalet, Copenhage• Hans Hasselbalch, Odense University Hospital

Finland• Tapani Ruutu, Helsinki University Central Hospital• Sakari Knuutila, University of Helsinki

France• Jean-Loup Huret, Université de Poitiers• François-Xavier Mahon, Université Victor Segalen, Bordeaux• Pierre Fenaux, Hopital Avicenne, Bobigny• Jean-Pierre Marie, Université Pierre et Marie Curie, Paris• Laurent Degos, Institut universitaire d'hématologie, Hôpital St. Louis, Paris• Norbert Ifrah, University of Angers• Guillaume Dighiero, Institut Pasteur, Paris• Xavier Troussard, Centre hospitalier universitaire de Caen• Claude Preudhomme, Centre hospitalier régional universitaire de Lille• Marie-Caroline Le Bousse-Kerdilès, Institut national de la santé et de la recherche médicale,

Villejuif• Marie-Christine Béné, Université Henri Poincaré, Nancy• Eliane Glickman, Association pour la recherche sur les transplantations médullaires, Paris• Catherine Cordonnier, Assistance publique-Hôpitaux de Paris, Créteil• Nicole Dastugue, Hôtel-Dieu Saint Jaques, Centre hospitalier universitaire de Toulouse• Fabienne Hermite, Ipsogen SAS, Marseille, SME

Germany• Dieter Hoelzer, University of Frankfurt• Ulrike Holtkamp, Deutsche Leukamie und Lymphom-Hilfe e.V., Bonn• Karl Überla, Ludwig-Maximilians-University Munich• Wolfgang Berdel, University of Muenster• Hartmut Döhner, University Hospital Ulm• Gerhard Ehninger, University Hospital Carl Gustav Carus, Technical University Dresden• Hans Heinrich Kreipe, Medizinische Hochschule Hannover• Dietger Niederwieser, Universitatsklinikum Leipzig• Carlo Aul, St. Johannes Hospital Duisburg• Norbert Gattermann, Universitätsklinikum Düsseldorf• Michael Hallek, University of Cologne• Andrew J. Ullmann, Johannes Gutenberg-Universitat, Mainz• Annette Schmitt-Gräff, Universitätsklinikum Freiburg• Winfried Gassmann, St.Marien-Krankenhaus Siegen gem. GmbH, Siegen• Wolf-Dieter Ludwig, Charité - Universitätsmedizin, Berlin• Harald Rieder, Philipps-University, Marburg• Jochen Harbott, Children's University Hospital, Justus-Liebig-Universitat, Giessen• Michael Kneba, University Hospital Schleswig-Holstein, Kiel• Lothar Kanz, Eberhard Karls Universitat, Tubingen• Justus Duyster, Technical University of Munich• Walter Fiedler, Universitätsklinikum Hamburg-Eppendorf• Einsele Hermann, Bayerische Julius-Maximilians-Universität, Würzburg

Hungary• Tamas Masszi, St. Laszlo Hospital, Budapest

Ireland• Michael O’Dwyer, University College Hospital Galway

Israel• Jacob Rowe, Fund for Medical Research Development of Infrastructure and Health Services,

Rambam Medical Center, Haifa• Alexander Levitzki, The Hebrew University of Jerusalem• Nurit Livnah, Peptor LTD, Rehovot

Italy• Gina Zini, Catholic University of Sacred Heart, Rome• Michele Baccarani, University of Bologna• Giuseppe Saglio, Università degli Studi di Torino• Sergio Amadori, Università degli Studi di Roma Tor Vergara• Roberto Foà, University "La Sapienza" of Rome• Tiziano Barbui, Ospedali Riuniti Di Bergamo• Federico Caligaris-Cappio, Università Vita-Salute San Raffaele, Milan• Carlo Bernasconi, Fondazione Collegio Ghislieri, Pavia• Giovanni Barosi, IRCCS Policlinico San Matteo, Pavia• Francesco Frassoni, Azienda Ospedaliera Ospedale San Martino, Genova• Cristina Mecucci, University of Perugia• Mariano Rocchi, Università degli Studi di Bari• Paolo Bernasconi, Università degli Studi di Pavia• Fabrizio Pane, CEINGE Biotecnologie avanzate SCARL, Napoli• Giuseppe Basso, Università degli studi di Padova• Sergio Ferrari, University of Modena and Reggio Emilia, Modena• Anna Locasciulli, Azienda Ospedaliera San Camillo Forlanini, Roma• Claudio Viscoli, University of Genova

Netherlands• Jacques van Dongen, Erasmus University Medical Center, Rotterdam• Theo De Witte, Stichting Katholieke Universiteit, University Medical Centre Nijmegen• G. J. Ossenkoppele, VU Academic Medical Center, Amsterdam• A.W. Dekker, University Medical Center, Utrecht• Marinus Van Oers, Academisch Ziekenhuis bij de Universiteit van Amsterdam• Roelof Willemze, Leiden University Medical Center

Poland• Andrzej Hellmann, Medical University of Gdansk• Aleksander Skotnicki, Jagiellonian University, Medical College, Krakow• Jerzy Holowiecki, Medical University of Silesia, Katowice• Jan Walewski, The Maria Sklodowska-Curie Memorial Cancer Center, Warsaw• Tadeusz Robak, Uniwersytet Medyczny w Lodzi, Lodz• Wieslaw Wiktor Jedrzejczak, Medical University of Warsaw

Romania• Nicolae-Dan Colita, Fundeni Clinical Institute, Bucharest

Russia• Valery Savchenko, National Research Center for Hematology, Moscow

Spain• Emili Montserrat, University of Barcelona• Juan Luis Steegmann, Hospital Universitario de la Princesa, Madrid• Miguel Sanz, Fundación Hospital Universitario "La Fe", Valencia• Jorge Sierra, Hospital de Sant Pau, Barcelona• José Maria Ribera, Hospital Universitari Germans Trias i Pujol, Badalona• Alberto Orfao, Universidad de Salamanca• Jesús M. Hernández, Fundación de Investigación del Cáncer de la Universidad de Salamanca

Sweden• Bengt Simonsson, University Hospital Uppsala• Per Ljungman, Karolinska Institutet, Stockholm• Bertil Hohansson, Lunds Universitet• Mats Brune, Göteborg University

Switzerland• Alois Gratwohl, University Hospitals, Basel• Andreas Tobler, University of Bern• Martine Jotterand, Centre Hospitalier Universitaire Vaudois, Lausanne

Turkey• Ibrahim Haznedaroglu, Ankara University

United Kingdom• Stephen O’Brien, University of Newcastle upon Tyne• Alan Burnett, University of Wales College of Medicine, Cardiff• Estella Matutes, Institute of Cancer Research, London• David Oscier, Royal Bournemouth Hospital• John Goldman, Imperial College of Science, Medicine and Technology, London• David Bowen, University of Dundee• Ghulam Jeelani Mufti, King's College London• Debra Mia Lillington, Queen Mary & Westfield College, London• Nicholas Cross, University of Southampton• John Reilly, The University of Sheffield• Khalid Tobal, Central Manchester and Manchester Children's University Hospitals• Rolf Apweiler, European Molecular Biology Laboratory, EBI, Cambridge• Katherine Ward, University College London


FURTHER IMPROVEMENT OF RADIOTHERAPY OF CANCER THROUGH SIDEEFFECT REDUCTION BY APPLICATION OF ADULT STEM CELL THERAPY

Proposal acronym FIRST EC contribution (€) 1.500.000Contract n° LSHC-CT-2004-503436 Instrument IPDuration (starting date) 2 years (01.09.04) Participants 8

Abstract:

Radiotherapy is the second most important treatment modality after surgery in the treatment of cancer. At present over50% of all cancer patients receive radiotherapy at one stage in their course. Inevitably normal tissues are also exposed toionising radiation during radiotherapy of tumours. This can result in organ failure and hence seriously can limit thetreatment dose. Reduction of the side effects of radiotherapy will not only increase the quality of life after the treatmentand but may also result in increased survival of cancer patients as it will allow dose-escalation to the tumour. This is trueeven if the most optimal physical dose-delivery (conformal therapy, protons) of radiation is applied. Radiation-induced(late) organ failure is mainly caused by stem cell sterilisation, leading to a reduced reconstitution of functional cells.Replenishment of the depleted stem cell compartment should allow regeneration of irradiated tissues. Multipotent stemcells have now been shown to reside in multiple adult tissues. For stem cell therapy purposes cells obtained from easyaccessible places as e.g. the skin and from bone marrow or peripheral blood appear ideal. The innovative vision of thisproject is to reduce radiation-induced complications through stem cell therapy. Hereto, 1) tissue specific adult stem cellswill be isolated, characterised and expanded, 2) non-specific bone marrow derived stem cells will be generated,mobilised, characterised and expanded 3) thus obtained stem cells will be tested for their capability to ameliorateradiation-induced complications in organs affected by radiotherapy 4) and potential risks will be assessed. A successfulreplacement of stem cells and subsequent amelioration of radiation-induced complications may open the road tocompletely new strategies in radiotherapy and help combating cancer.

Web site: http://www.euproject-first.org

Participants:

Coordinator

Netherlands

Dr Robert Coppes, University of Groningentel: +31 50 363 27 09 fax: +31 50 363 29 [email protected]

Denmark• Thue W. Schwartz, 7TM Pharma A/S, Hoersholm, IND

France• Michèle Martin, Commissariat à l'Energie Atomique, Paris• Pierre Charbord, Université François Rabelais, Tours• Dominique Pierre Thierry, Institut Radioprotection et Sureté Nucléaire, Fontenay-aux-roses

Germany• Wolfgang Dörr, University of Technology, Dresden

Netherlands• Jan Wondergem, Leiden University Medical Center

United Kingdom• Mohi Rezvani, Chancellor Masters and Scholars of the University of Oxford


REPROGRAMMING THE IMMUNE SYSTEMFOR THE ESTABLISHMENT OF TOLERANCE

Proposal acronym RISET EC contribution (€) 10.000.000Contract n° LSHB-CT-2004-512087 Instrument IPDuration (starting date) 5 Years (01.03.05) Participants 22

Abstract:

Transplantation dramatically improves the survival of patients with end-stage failure of vital organs. However, as a directconsequence of the immunosuppressive drugs permanently required to prevent rejection, recipients have a significantlyincreased risk of infection and malignancies Moreover, these drugs are expensive, do not prevent long-term damage ofthe graft, and exert toxic effects outside the immune system. The induction of transplant tolerance, defined as permanentacceptance of the graft in absence of continuous immunosuppression, would be a major step forward Recent advancesin post-genomic immunology suggest that this goal is achievable in a near future. Indeed, new biotechnology productshave been shown to promote long-term transplant acceptance in pre-clinical models. RISET will focus on the translationof these advances into industrial development and clinical practice First, diagnostic tests to identify transplanted patientsfor whom immunosuppressive treatment could be safely minimized or withdrawn will be developed. These tests will beapplied to patients under conventional treatment as well as to patients enrolled in pilot clinical investigations based oncellular products with potential for tolerance induction. Because of the nature of this research, effective communicationwith patient organizations and regulatory bodies will be organized, and related ethical and societal questions will bespecifically addressed. In parallel, relevant models of tolerance will be used to identify new genes, molecules or celltypes that will form the basis for novel diagnostics and therapeutic approaches. The exploitation of the knowledgecreated in RISET will be facilitated by the inclusion of several SMEs in the consortium and the creation of an industrialplatform. In order to exploit innovative concepts emerging outside the consortium, RISET will be open to new industrial oracademic partners for which a budget has been provisioned.

Web site: http://www.risetfp6.org

Participants:

Coordinator

Belgium

Prof. Michel Goldman, Departement Immunologie Experimentale, Universite Libre de Bruxellestel: +32 25556138 fax: +32 [email protected]

Belgium• Anne-Marie Priells, Tech-Know Consultants SPRL, Koksijde, Waterloo, SME

Czech Republic• Jiri Lacha, Department of Nephrology, Transplantcentre IKEM, Transplant Laboratory, Centre of

Experimental Medicine IKEM, lnstitute for Clinical and Experimental Medicine, Prague

France• Marina Guillet, TcLand, Nantes, SME• Lucienne Chatenoud, Laboratoire d'Immunologie Biologie - UFR Necker Enfants Malades -

Hopital Necker Enfants Malades, Universite Rene Descartes, Paris• Anne Cambon-Thomsen, lnserm U 558 - Epidemiologie et analyses en sante publique, Faculte de

Medecine, lnstitut National de la Sante et de la Recherche Medicale, Toulouse• Jean-Paul Soulillou, INSERM U437 / ITERT, Centre Hospitalier de Nantes, Nantes

Germany• Uwe Janssen, Memorec Biotec GmbH, Cologne, IND• Ulrich Kunzendorf, Division of Nephrology & Hypertension, University of Schleswig-Holstein, Kiel• Albrecht Wendel, Steinbeis Technology, Transfer Center for ln-vitro Pharmacology & Toxicology,

Konstanz, SME• Fred Faendrich, Dept. of General and Thoracic Surgery, University of Schleswig-Holstein,

BLASTICON GmbH Biotechnology Company, Kiel, IND• Hans-Dieter Volk, Dept of Medical Immunology, Charité Universitätsmedizin Berlin, Berlin• Bernd Arnold, Tumor lmmunology / Molecular lmmunology, Deutsches Krebsforschungszentrum,

Heidelberg

Israel• Yair Reisner, lmmunology-Biology, Weizmann lnstitute of Science, Rehovot

Italy• Maria Grazia Roncarolo, Hsr-Tiget, Fondazione Centro San Raffaele Del Monte Tabor, Milan• Luciano Adorini, Bioxell S.P.A., Milano

Netherlands• Mohamed R. Daha, Department of Nephrology, Leiden University Medical Center, Leiden

Spain• Blanca Miranda Serrano, National Transplant Coordination, Organización Nacional de

Trasplantes, Madrid

Switzerland• Robert Rieben, Department of Clinical Research, Cardiology, University of Bern Hospital, Bern

United Kingdom• Kathryn Jayne Wood, Nuffield Department of Surgery, Masters & Scholars of the University of

Oxford• Herman Waldmann, Sir William Dunn School of Pathology, University of Oxford• Robert Lechler, Department of lmmunology, Faculty of Medicine, lmperial College London,

London


THE DEVELOPMENT OF NEW DIAGNOSTIC TESTS, NEW TOOLS AND NON-INVASIVE METHODS FOR THE PREVENTION, EARLY DIAGNOSIS AND MONITORING

FOR HAEMATOPOIETIC STEM CELL TRANSPLANTATION

Proposal acronym STEMDIAGNOSTICS EC contribution (€) 2.500.000Contract n° LSHB-CT-2007-037703 Instrument SME-STREPDuration (starting date) 3 years (01.04.07) Participants 13

Abstract:

Over 7000 allogeneic haematopoietic stem cell transplants (HSCT) are carried out each year in Europe alone, as atreatment for leukaemia and lymphoma. Techniques and cure rates are improving but the overall survival rate remainsbetween 40-60%.This project will develop new proteomic, biological and genomic tests and tools for early diagnosis and monitoring ofpatient response to novel therapeutics for the most severe complication of HSCT; graft versus host disease (GvHD) andwill bring to the clinic a new generation of diagnostics that will significantly improve HSCT therapy and patient outcome.The Consortium unites 5 European SMEs with expertise and markets in genomic and proteomic testing, diagnostic assaydevelopment and biochips, with clinical partners selected for their world leading research in HSCT and access to clinicalsamples and patient groups.The project will focus on the role of relevant genes and biomarkers associated with acute and chronic GvHD, usingretrospective samples from established biobanks and prospective clinical trials to: 1) Identify novel bio and genomicmarkers for diagnostics; 2) Develop novel diagnostic tools using genomics, proteomics, in vitro bioassays and biochips; 3)Test the new diagnostics in animal models & on clinical samples; 4) Exploit the new tools for commercial use.

The above will be realised by: 1) Development of diagnostic tests using single nucleotide polymorphism (SNP) analyses(SME IMGM), based on results from previous EC funded research (EUROBANK, TRANSEUROPE); 2) Using proteomicsvia mass spectrometry (evaluation/development of diagnostic patterns (SME MOSAIQUES), ELISA kits (SME APOTECH)and protein biochip prototypes (SME ORLA), for the development of fast high throughput technologies. 3) Development ofnovel reagents for monitoring graft versus leukaemia, GvHD and targeted therapy (SME MULTIMUNE; SMENASCACELL). 4) Comparative studies in an autoimmune disease model of inflammation; rheumatoid arthritis.

Web site: not yet

Participants:

Coordinator

United Kingdom

Prof. Anne Dickinson, Haematological Sciences School of Clinical and Laboratory Sciences,The Medical School, University of Newcastle upon Tynetel: +44 191 282 4259 fax: +44 191 222 [email protected]

Austria• Hildegard Greinix, Universitaetsklinik fuer Innere Medizin 1, Medical University of Vienna, Vienna

Czech Republic• Ilona Hromadnikova, Cell Biology Laboratory, 2nd Medical Faculty, Charles University, Prague

France• Gerard Socie, Service d'Hematologie Greffe de Moelle, Hospital Saint Louis, Paris

Germany• Ernst Holler, Dept. Hematology/Oncology, University of Regensburg, Klinikum der Universitaet

Regensburg, Regensburg• Harald Mischak, Mosaiques Diagnostics GmbH, Hannover, SME• Gabriele Multhoff, Department of Hematology and Oncology, University Hospital Regensburg,

multimmune GmbH, Regensburg, SME• Ralph Oehlmann, IMGM Laboratories GmbH, Martinsried, SME• Hans-Jochem Kolb, Klinical Cooperation Group Hematopoietic Cell Transplantation, Institute of

Molecular Immonology, Forschungszentrum fuer Umwelt und Gesundheit, GmbH, Muenchen

Switzerland• Lars French, Dermatology, Geneva University Hospital & Louis Jeanet Skin Cancer Lab,

University Medical Centre, University of Geneva• Maximilien Murone, Apotech Corporation, Epalinges

United Kingdom• Amanda McMurray, Technology, Centre of Excellence for Nanotechnology, Micro & Photonic

Systems, Newcastle upon Tyne• Dale Athey, Nanotechnology Centre, Orla Protein Technologies Ltd, Newcastle upon Tyne, SME


IDENTIFICATION OF GENOMIC AND BIOLOGICAL MARKERSAS PREDICTIVE/DIAGNOSTIC/THERAPEUTIC TOOLS

FOR USE IN ALLOGENEIC STEM CELL TRANSPLANTATION:TRANSLATIONAL RESEARCH TOWARDS INDIVIDUALISED PATIENT MEDICINE

Proposal acronym TRANS-NET EC contribution (€) 4.539.456Contract n° MRTN-CT-2004-512253 Instrument Marie-Curie RTNDuration (starting date) 4 years (01.01.2005) Participants 12

Abstract:

Allogeneic stem cell transplantation (HSCT) is a life saving therapy for haematological disorders (leukaemia andlymphoma, inherited immune disorders, and a plastic anaemia). Over 7000 such transplants are carried out each year inEurope. However the overall survival rate after HSCT is poor (40-60%), and cure of patients is hampered by clinicalcomplications that arise post-transplant; largely due to genetic and biological differences which exist between a givenpatient and donor. These differences include transplantation antigens (major and minor histocompatibility antigens).Pioneering research by Partners, have indicated that a number of non-HLA gene polymorphisms also affect the severityand incidence of transplant related complications. There is an urgent need to improve patient-donor matching at both thebiological and genomic level which would develop HSCT beyond the current state of the art. HSCT outcomes will beimproved if predictive assays, diagnostic tools and new therapeutics were developed and ultimately used by HSCTclinicians for individual patient based medicine. TRANS-NET teams have expertise in predictive bioassays, genomics,diagnostics and novel therapeutics who will train researchers in the key technologies of, mRNA expression profiling,pathology, non-HLA immunogenetics and mechanisms of immune recognition; with the ultimate aim of applying theresults of TRANS-NET in the HSCT clinical setting. TRANS-NET aims to: 1) Define new biological/genomic indicatorsand novel therapies for the potential development of new clinical strategies for improving the outcome and quality of lifeof HSCT patients; 2) Develop unique training programmes in genomics and immunobiology of transplantation andgenerate highly trained scientists with the ability to manage complex projects and understand the scientific challenges ofindividualised patient medicine; 3) Disseminate knowledge gained throughout the ERA and clinical HSCT centres acrossthe EC.

Web site: http://www.trans-net.org.uk

Participants:

Coordinator

United Kingdom

Prof. Anne Dickinson, Haematological Sciences, School of Clinical and Laboratory Sciences,University of Newcastle-Upon-Tynetel: +44 191 282 4259 fax: +44 191 222 [email protected]

Austria• Hildegard Greinix, Bone Marrow Transplantation Unit, Medical University of Vienna

Czech Republic• Ilona Hromadníková, 2nd Medical Faculty, Charles University, Prague

France• Nuala Mooney, INSERM U396, Immunogénétique Humaine, Centre de Recherches Biomédicales

des Cordeliers, Paris

Germany• Ralf Dressel, Abt. Immungenetik, "Bereich Humanmedizin" Georg-August-University Goettingen• Ernst Holler, Hamatology und Internistiche Onkologie, Klinikum der Universität Regensburg &

Gabriele Multhof, Department of Hematology and Oncology, University of Regensburg• Hans Jochem Kolb, Klinikum Großhadern, Stammzelltransplantation, Ludwig Maximillian

Universität Medizinische Klinik III, München• Markus Uhrberg, Institut fuer Transplantationsdiagnostik und Zelltherapeutika,

Universitätsklinikum Düsseldorf, Heinrich-Heine-Universitat, Dusseldorf

Norway• Bent Rolstad, BM Transplantation Group, Dept. Anatomy, University of Oslo

Switzerland• Lars French, Department of Dermatology, Geneva University Hospital, University of Geneva

United Kingdom• Mark Lawler, Cancer Molecular Diagnostics, CPL St James's Hospital, Dublin• Walter Kolch, Institute of Biomedical and Life Sciences, University of Glasgow


TRANSPLANTATION RESEARCH INTEGRATION ACROSS EUROPE

Proposal acronym TRIE EC contribution (€) 450.000Contract n° LSSB-CT-2007-037540 Instrument SSADuration (starting date) 1.5 year (01.03.07) Participants 5

Abstract:

The overall objective of TRIE is to help realise ERA objectives by preparing the groundwork for an integrated, large-scaleinitiative in transplantation research in the European Union.This will be achieved through:1. Identifying transplantation research topics which are best addressed by an integrated European action i.e. topics whichcannot be adequately addressed at national level.2. Confirming political and research funding agency support at national level for: Centralising existing programmes inthese fields; Committing funds to new centralised programmes.3. Identifying the common denominators on which a joint European initiative will be based and deciding on an optimalinstrument for a future integrated initiative;4. Preparing detailed implementation plans, both scientific and organisational so that these plans can be made operationalfollowing the mid-term review of FP7;5. Presenting the final results and implementation plans at a high profile event at the European Parliament.

Building such a novel integrated transplantation research programme across Europe depends on a careful and stepwiseprocess involving key stakeholders, national research policy authorities, as well as the current ERA-NET project Alliance-O. This cooperation will be assured through the establishment of two Advisory bodies: a Scientific Council made up ofleading research scientists in the transplant field and a Stakeholders Forum made up of political representatives atEuropean and national level, research agencies and funding bodies, academics, industry, patient organisations and othersuch groups.The TRIE proposal has already generated widespread European interest at both political and scientific level. Elevenleading scientists in transplantation research have pledged their commitment to the aims and activities of the ScientificCouncil and letters of support for this initiative have been received from public research agencies in nine EU countries.

Web site: not yet

Participants:

Coordinator

Belgium

Prof. Michel Goldman, Institut d'Immunologie Médicale, Universite Libre de Bruxelles, Charleroi(Gosselies), Bruxellestel: +32 2 650 95 60 fax: +32 2 650 95 [email protected]

Ireland• Siobhan McQuaid, International Projects Department, ABU International Project Management

Limited, Dublin, SME

Spain• Blanca Miranda Serrano, National Transplant Coordination, Centro Nacional de Trasplantes y

Medicina Regenerativa, Madrid

United Kingdom• Kathryn, WOOD, Nuffield Departement of Surgery, University of Oxford, The Chancellor, Masters

and Scholars of the University of Oxford, Oxford• Alejandro Madrigal, The Anthony Nolan Research Institute, The Anthony Nolan Trust,

Hampstead, London


INTEGRATING

Ethical, legal & societal aspects, training

A EUROPEAN MULTIMEDIA REPOSITORY OF SCIENCE

Proposal acronym EMRS EC contribution (€) 675.000Contract n° LSHM-CT-2004-504755 Instrument SSADuration (starting date) 4 years (01.08.04) Participants 5

Abstract:

Life sciences hold promise to improve the quality of life in our society. Because of the complexity of the field, scientific,social and ethical uncertainties remain about many of the possible technological applications. Unresolved concerns maylead to rejection of beneficial technologies with negative impact on innovation and socio-economic fabric of our society.Constructive dialogue with the key stakeholders is needed to minimise unfounded concerns and maximise publicempowerment on these complex issues, while at the same time, allowing a positive feedback to assure that science ismoving forward in cohort with social needs and expectations. The European Multimedia Depository of Science (EMRS)will make a strong effort to bring the scientific world closer to three chosen key stakeholders: the general public,educators and media. EMRS will address European co-ordinated LifeSciHealth scientific activities in the area ofadvanced genomics, its application for health and combating of major diseases. This will be done through a number ofapproaches and deliverables. The chosen stakeholders will be reached by using effective communication platforms thatoffer high impact value: video, multimedia, television, internet and publishers.The main deliverables of the project aresixteen high quality short films. There will be three levels of disseminating the film contents: i) through broadcastingmedia, namely Discovery Channel and European Broadcasting Union; ii) using an on-line internet based multimedialibrary and iii) by direct distribution of VHS, CD- ROM and DVD to target groups through our four associated networksand members of our extensive advisory board. In support of these activities two additional actions will be undertaken:creation of internet based Rapid Response Science Network (RRSN) where scientists will answer questions related tothe topics addressed in the project and three focus meetings with proceedings to be published by Springer.The first lot of 4-5 minute films are based on a number of current EU integrated projects, covering cell differentiation(primarily stem cells). Film 1 deals with new advances in stem cell research - therapeutic angiogenesis - where bonemarrow epithelial progenitor cells are injected into the heart tissue of heart attack patients to encourage vesselregeneration. Film 2 addresses the science behind vessel regeneration, looking especially at zebra fish. Film 3 dealswith the theory of cell differentiation, the so called epigenetic code. The second lot will concern twin studies, and life styleissues (exercice, nutrition and diabetes). The third lot will be programmed according to the feedback to the first ones.

Web site: http://www.eusem.com

Participants:

Coordinator

France

Dr. Paul Pechan, Ludwig Maximilians University, Munichtel: +49 816 171 342 1 fax: +49 816 171 451 [email protected]

Austria• Barbara Streicher, Dialog<>gentechnik, Vienna

Germany• Heidi Bohle, Visions Unlimited Medien GmbH, Otterfing

Ireland• Catherine Adley, Biotechnology Awareness Centre, University of Limerick

Netherlands• Gerhard Ernst de Vries, ProBio Partners VOF, Overschild

Commission: Directorate General for Research - Health Directorate - Unit F1 Strategy and Policy

EUROPEAN HUMAN EMBRYONIC STEM CELL REGISTRY

Proposal acronym EU hESC registry EC contribution (€) 1.000.000Contract n° LSSM-CT-2006-037820 Instrument SSADuration (starting date) 3 years (01.03.07) Participants 13

Abstract:

Human embryonic stem cell (hESC) research holds promise for the development of therapies for degenerativepathologies, offers a tool for drug discovery and toxicity tests, for studying human development, disease physiology andgene control. hESC lines are currently derived in an increasing number of laboratories in Europe and around the world. Adetailed registry of available cell lines will promote the validation and efficient use of these precious cells for research andapplication. Comparable information is needed about the origin of the cell lines, the methodology and standards for theirderivation and the characteristics to assess their availability for research and future therapies. The growing use of hESCby the scientific community demands a high quality and comprehensive registry. The aim of the proposed European hESCregistry is to promote access to all hESC lines derived in Europe and transparency about their characteristics. Only welldefined and adequately characterised hESC lines according to the parameters established by the registry be listed. Todetermine listing decisions, the features of the cell lines will be evaluated according to defined scientific and qualitystandards. Data such as the origin, the derivation methodology, as well as the different parameters used forcharacterisation will be recorded for each hESC line in the registry. Contact data and legal status will also be available foreach cell line. Each cell line will be annotated with essential and useful information on their characteristics andapplications. Registry of the database and website will facilitate the continuous mapping of the research and legislativelandscapes in a topographical online design. The registry will also serve as a communication and consultation platform forhESC researchers, clinical groups, patients groups and the public at large for information on hESC.

Web site: http://www.cellnet.org/ (menu: networks > hESC-Registry)

Participants:

Coordinator

Germany

Dr. Joeri Borstlap, Dep. of Experimental Surgery, Charité, Universitätsmedizin Berlintel: +49 30 450 552 501 fax: +49 30 450 576 [email protected]

Belgium• Karen Sermon, Research Group Reproduction and Genetics, Vrije Universiteit Brussel

Czech Republic• Petr Dvorak, Department of Molecular Embryology, Institute of Experimental Medicine, Academy

of Sciences of the Czech Republic, Prague

Finland• Timo Tuuri, Biomedicum Helsinki

France• Carine Camby, Agence de la Biomedecine, St Denis La Plaine

Germany• Andreas Kurtz, Licensing office for human embryonic stem cell research and head, stem cell lab,

Robert Koch-Institut, Berlin

Israel• Benjamin Reubinoff, The Hadassah Human Embryonic Research Center, Hadassah University

Hospital, Jerusalem

Netherlands• Christine Mummery, Hubrecht Laboratory, Utrecht

Spain• Anna Veiga, Stem Cell Bank, Centre de Medicina Regenerativa / Institut Dexeus, Barcelona• Agustín G. Zapata, Instituto de Salud Carlos III, Madrid

Sweden• Outi Hovatta, Department of Clinical Science, Karolinska Institutet, Karolinska University Hospital

Huddinge, Stockholm

Turkey• Necati Findikli, ART & Reproductive Genetics Centre, R&D Laboratory, Istanbul Memorial

Hospital, Sisli/Istanbul

United Kingdom• Glyn Stacey, U.K. Stem Cell Bank, National Board for Biological Standards, South Mimms


EUROPE, ITS CITIZENS AND STEM CELL RESEARCH: A ONE-DAY CONFERENCE

Proposal acronym EUROCITS EC contribution (€) 500.000Contract n° LSSM-CT-2005-018699 Instrument SSADuration (starting date) 16 Months (01.07.05) Participants 1

Abstract:

To organise a one-day conference of estimated 500 participants providing the latest scientific information on the researchon and use of Stem Cells in severe disorders. The goal of this conference is to promote a real dialogue on stem cellresearch between science and society. The understanding of most of the European population on the topic of stem cellresearch and its potential is limited. They need help to focus on research priorities, ethical questions and to contribute toan informed debate. Patients, as citizens of Europe, will be able to debate with other stakeholders some of the basicethical challenges underpinning this research and its application. The conference will use lay language and there will beample opportunity to pose questions to experts in this very sensitive field of research. Similar conferences have beenorganised in the past by scientists for scientists but this event will be planned with particular focus on the impact ofresearch on patients. EFNA, the European Federation of Neurological Associations, an umbrella organisation for pan-European patient federations in the field of brain disorders, will be the organiser. Patients from a wide range of disorders,carers, health professionals, scientists, ethicists, politicians, media, employers and health insurers will be invited to takepart. The event will be held in Brussels with free registration. The working language will be English, with simultaneoustranslation into makor EU languages. The newly-integrated EU countries will have active participation by speciallyenabling them to take part in the event. To maximise the results, the conference proceedings will be disseminated throughradio and TV transmissions, websites, and publications in popular and scientific journals, newsletters and on CD-rom. It isintended that this conference will lead to clearer understanding of the issues surrounding stem cell research and anintegrated way forward in Europe to benefit the European citiziens.

Web site: http://www.erastepps2005.eu.com

Participant:

Coordinator

Belgium

Mrs Mary G. Baker, European Federation of Neurological Associations (EFNA), Brusselstel: +39 0554 362 098 fax: +39 0554 271 [email protected]


CHIMERAS AND HYBRIDS IN COMPARATIVE EUROPEAN AND INTERNATIONALRESEARCH – SCIENTIFIC, ETHICAL, PHILOSOPHICAL AND LEGAL ASPECTS

Proposal acronym imgbchimerashybrids EC contribution (€) 600.424Contract n° SAS6-CT-2005-016708 Instrument CADuration (starting date) 2 years (01.10.05) Participants 23

Abstract:

The objective of the proposed project is to develop a deeper and comprehensive understanding of the fundamentalproblems in the research on Chimeras and Hybrids by means of a European and International aligned exchange and apartnership of co-operation, dialogue and network with Scientists from the ranges of the natural sciences, ethics,philosophy and jurisprudence, as well as with External Agents from Society under the co-ordination of the IMGB. The newand partly still unconsidered problem complex of mixing creatures and blending techniques of human being and animals isat the centre of attention in natural scientific, ethical, philosophical and legal analysis. The interdisciplinary andinternational analysis and examination of human being - animal Chimera and Hybrid formations includes thereforefundamental and basic problem complexes in each research discipline, such as the creation possibilities and differentkinds of characteristics of Chimeras and Hybrids, the production of hybrid ES-cells, the creation and the use of transgenicanimals, the open questions of potential therapies, the ethical and moral evaluation, as well as the constitutional and legalaspects of human dignity, freedom of research and protection of animals. The realisation of the objective will be achievedby compiling concepts, proposals for research practices, recommendations and decision supports for decision makers,thus enabling a structural and enduring interrelation between rapid progress in scientific research and basic legal, ethicaland philosophical principles. By means of reports and different elements of dynamic interaction, through speeches anddiscussions on basic and specific problems in the framework of Conferences and Workshops for compiling a finalsynthesis report, the proposal will bring Science and Society closer together and will also stimulate the development ofemerging questions on Chimeras and Hybrids in the European Research Area.

Web site: http://www.chimbrids.org

Participants:

Coordinator

Germany

Prof. Dr. Jochen Taupitz, Universität Mannheim, Institute for Medical Law (IMGB), Mannheimtel: +49 621 181 1934/1990 fax: +49 621 181 [email protected]

Austria• Erwin Bernat, Universität Graz, Institute for Civil Law, Foreign and International Private Law, Graz

Belgium• Walter Lesch, Université Catholique de Louvain, Faculty of Theology and Canon Law, LLN

Canada• Bartha-Maria Knoppers, Université de Montréal, Centre de Recherche en Droit Public, Montréal• Derek van der Kooy, University Toronto, Department of Medical Genetics & Microbiology, Toronto

China• Kuisheng Dai, University of Nanjing, German Institute for Business Law, Nanjing• Qi Zhou, Chinese Academy of Science, Institutee of Zoology, Beijing

Czech Republic• Filip Krepelka, Masarykova unverzita v Brno, Brno• Josef Kure, Masarykova unverzita v Brno, Brno

France• Sonia Desmoulin, Univ. Paris I, Centre Recherche Droit des Sciences et des Techniques, Paris• Jean-Paul Renard, INRA, Départ. Physiologie animale & systèmes d'élevage, Jouy-en-Josas

Germany• Michael Bader, Max-Delbrück-Centrum Berlin, Institute or Department, Town• Jan C. Joerden, Europa-Universität-Viadrina Frankfurt, interdisciplin. Center for Ethics, Frankfurt• Eckhard Wolf, Ludwig-Maximilians-Universität München, Veterinary School, München

Hungary• Andras Dinnyes, Agricultural Biotechnology Center, Institute or Department, Town

Israel• Amos Shapira, Tel Aviv University, Law Faculty, Tel Aviv

Japan• Motomu Shimoda, Osaka University, Osaka School of International Public Policy, Osaka• Fumio Tokotani, Osaka University, Osaka School of International Public Policy, Osaka

Netherland• Marcus Duewell, Universiteit Utrecht, Institute for Ethics, Utrecht

Spain• Carlos Maria Romeo-Casabona, Universidad de Deusto, Chair BBVA Foundation Provincial

Government of Biscay in Law and the Human Genome, Bilobao/Donostia

Sweden• Elisabether Rynning, Uppsala Universitet, Faculty of Law, Uppsala

Switzerland• Rainer Schweizer, Universität St.Gallen, Law School, St Gallen

United Kingdom• Deryck Beyleveld, University Sheffield, Sheffield Institute for Biotechnological Law and Ethics,

Sheffield

United States• Autumn Fiester, University Pennsylvania, Institute or Department, Town• Timothy Jost, Washington and Lee University, Law School, Lexington, VA

Commission: Directorate General for Research - Science & Society Directorate - Unit C3 Ethics

EUROPEAN LABCOURSE: ADVANCED METHODS FOR INDUSTRIAL PRODUCTION,PURIFICATION AND CHARACTERISATION OF GENE VECTORS

Proposal acronym INDUSTRYVECTORTRAIN EC contribution (€) 176.000Contract n° LSHB-CT-2003-505516 Instrument SSADuration (starting date) 21 months (01.01.2004) Participants 2

Abstract:

To allow gene & cell therapies to evolve more quickly into biomedical sciences, it is necessary to disseminate throughout thescientific community: (i) the basic knowledge of the biology of vectors and stem cells, (ii) the expertise of their production,purification and characterisation, (iii) the assessment of their therapeutic efficiency and bio-safety (iv) the definition of theregulatory frames in which these tools can be transformed into new medicines and commercially exploited. The state of thisevolution is today still far from its objective, since the insufficient knowledge of the biology of vectors and stem cells, a scarceco-ordination of research projects and the absence of integration of the activities of the actors operating in different concernedareas (research, industry, health products regulation and marketing). Therefore, the realisation of a multidisciplinary trainingprogramme, which integrates various scientific and technological approaches, is necessary today to address a real need ofthe scientific community. The activity scheduled in this proposal concerns a 2-weeks theoretical and practical course, where32 young researchers (selected on the basis of scientific excellence) will be trained on the advanced processes of vectorproduction, purification and quality control for gene therapy clinical trials. The course is expected to gather young scientistsfrom industrial and academic institutions, coming from several EU and candidate countries. It will present training andscientific innovations: for the first time the various aspects of the development of vector technology from the bench to theindustrial level will be provided to the community. Theoretical modules will be open to large public, namely, biotech firms andregulatory agencies, where the status of the art will be presented and discussed. The course will (a) allow young researchersfrom industries and academia to acquire a multidisciplinary training on vectors development, the definition of new ethical andlegal frames, and socio-economical implications; (b) implement an environment in which all concerned institutions (public andprivate) and regulatory agencies will exchange respective expertise to develop process towards the economical exploitation ofnew therapeutic tools and processes.

Web site: http://www.vecteurotrain.org

Participants:

Coordinator

France

Dr. Mauro Mezzina, GENETHON, Evrytel: +33 1 6947 1023 fax: +33 1 6077 [email protected]

France• Gilles Waksman, Universite de Evry-Val d'Essonne, Evry


EUROPEAN LABCOURSE : TOWARDS CLINICAL GENE THERAPY :PRECLINICAL GENE TRANSFER ASSESSMENT

Proposal acronym INVIVOVECTORTRAIN EC contribution (€) 161.620Contract n° LSHB-CT-2003-503219 Instrument SSADuration (starting date) 21 months (01.07.03) Participants 2

Abstract:

To allow gene & cell therapies to evolve more quickly into biomedical sciences, it is necessary to disseminate throughout thescientific community: (i) the basic knowledge of the biology of vectors and stem cells, (ii) the expertise of their production,purification and characterisation, (iii) the assessment of their therapeutic efficiency and bio-safety with an adequate animalexperimentation, (iv) the definition of the regulatory frames in which these tools can be transformed into new medicines andcommercially exploited. The state of this evolution is today still far from its objective, since the insufficient knowledge of thebiology of vectors and stem cells, a scarce co-ordination of research projects and the absence of integration of the activities ofthe actors operating in different concerned areas (research, industry, health products regulation and marketing). Therefore,the realisation of a multidisciplinary training programme, which integrates various scientific and technological approaches, isnecessary today to address a real need of the scientific community. The activity scheduled in this proposal concerns a 2-weeks theoretical and practical course, where 32 young researchers (selected on the basis of scientific excellence) will betrained on the basic procedures of gene transfer into animals, targeting major organs (liver, brain, muscle, lung), and ofimaging-monitored gene expression in alive animals. The course is expected to gather young scientists of academic andindustrial institutions, coming from several EU and candidate countries. It will present training and scientific innovations: for thefirst time the vector production technology will be combined with the in vivo evaluation. Theoretical modules will be open tolarge public, namely, biotech firms and regulatory agencies, where the status of the art will be presented and discussed. Thecourse will (a) allow young researchers from academia and industries to acquire a multidisciplinary training on vectorsdevelopment from bench levels to medicines, including the industrial development and the definition of new ethical and legalframes; (b) implement an environment in which all concerned institutions (public and private) and regulatory agencies willexchange respective expertise to develop process towards the economical exploitation of new therapeutic tools andprocesses.

Web site: http://www.vecteurotrain.org

Participants:

Coordinator

France

Dr. Mauro Mezzina, GENETHON, Evrytel: +33 1 6947 1023 fax: +33 1 6077 [email protected]

Spain• Miguel Chillon Rodriguez, Universitat Autonoma de Barcelona (UAB)


REPROGENETICS: THE ETHICS OF MEN MAKING MEN

Proposal acronym REPROGENETICS (CLEMIT) EC contribution (€) 980.000Contract n° SAS6-CT-2003-003286 Instrument STREPDuration (starting date) 3 years (01.04.04) Participants 6

Abstract:

During the last 5 years genetics and reproductive medicine have merged to form Reprogenetics and come to representrevolutionary possibilities for studying grave diseases and developing new therapies. Specific scenarios are developedthat may result in the technical possibility to change the genetic constitution of humans and their descendants. In fact, ina limited way, some technologies may already do this.The overwhelming possibilities presented by such developments have been met with concern and reignited the debateon the question if men might be able to design and change the genetic structure of other men and if men may be able tocreate new human beings.The values at stake in these issues are often felt as deeply human and there is a widespread conviction that several ofthe new technical possibilities should be banned or at least placed under moratorium no matter how promising they maybe. The situation of a moratorium or ban might create a false impression of ethical clarity and yet, the content andstrength of ethical arguments applied has not yet been analysed or made explicit. When not accompanied by aconsistent study of conditions under which it may be lifted, a moratorium would no longer be a sign of ethical strength butof indecisiveness and a lack of ethical decision-making. Still in circles of private and academic research not guided byethical and social reflection, but as an arbitrary result of unknown market forces and the private ambition of researchersand research institutes.The project will make a comparative analysis of the ethical aspects of hot issues in gene therapy and cloning, study theambiguities and inconsistencies of current law and theory, try to strengthen them and, when needed, distinguish contextsthat share names, but may have completely different ethical implications.

Web site: http://www.clemit.net

Participants:

Coordinator

Belgium

Prof. Guido Van Steendam, International Forum for Biophilosophy, Leuventel: +32 16 23 11 74 fax: +32 16 29 07 [email protected]

France• Jacques Mallet, Laboratoire de Genetique Moleculaire de la Neurotransmission et des Processus

Neurodegeneratifs, Centre National de la Recherche Scientifique, Paris

Italy• Cinzia Caporale, Einaudi, Universita degli Studi di Roma “La Sapeinza”, Rome

Norway• Matthias Kaiser, National Committees for research Ethics, NENT, Oslo

Spain• J. Carlos Romeo Casabona, Catedra Interuniversitaria Fundacion BBVA - Diputacion Foral de

Bizkaia, de Derecho y Genoma Humano, Universidad del Pais Vasco (UPV/EHU), Bilbao

United Kingdom• John Harris, Institute of Medicine Law and Bioethics (IMLAB), The Victoria University of

Manchester

Commission: Directorate General for Research - Science & Society Directorate - Unit C3 Ethics and Science

FROM CELLULAR SENESCENCE AND CELL DEATH TO CANCER AND AGEING

Proposal acronym SENECA EC contribution (€) 142.800Contract n° LSHM-CT-2006-037312 Instrument SSADuration (starting date) 2 years (01.10.06) Participants 3

Abstract:

Age is the most important demographic risk factor for many life-threatening human cancers. About two-thirds of alldiagnosed cancers occur in people over the age of 65. Since tumours include cancer cells with an extensive proliferativehistory, subject to senescence and senescence-avoidance mechanisms, cancer researchers commonly study variousaspects of biological ageing. However, many cancer specialists, clinicians, and industry representatives remain unawareof what ageing research can offer for cancer prevention and therapy. Presently the research fields of biological ageingand cancer in Europe remain largely fragmented, without structured links or widespread interdisciplinary approaches.Therefore, the main goal of the planned 2_-day, 300-participant conference is to improve the awareness of ageingresearch among cancer researchers and stimulate cooperation aimed at redefining molecular targets and improvingcancer prevention and therapeutics in the ageing population. The conference will provide a forum for scientific exchangeamong outstanding European scientists working in the fields of ageing and cancer. The discussion will focus around suchissues as: DNA damage, telomeres and telomerase in cancer and ageing, effects of tissue environment in tumourformation, impact of the ageing immune system on cancer immunosurveillance and immunotherapy, links between stemcells and cancer and ageing, links between tumour suppression and cellular senescence, and cellular senescence as anew target in anticancer therapy. The conference will also bring together other key stakeholder groups such as policymakers, clinicians and industry.The proposed event will contribute to attracting scientists from cancer research and other disciplines to ageing research. Itwill help establish sustainable organizational links between these two closely related scientific fields, structuring Europeanresearch in oncogerontology.

Web site: http://www.seneca2007.eu

Participants:

Coordinator

Poland

Prof. Ewa Sikora, Department of Cellular Biochemistry, Laboratory of Molecular Bases of Aging,Instytut Biologii Doswiadczalnej im. M. Nenckiego Polskiej Akademii Nauk, Warsawtel: +48 22 589 2436 fax: +48 22 589 [email protected]

Germany• Graham Pawelec, Innere Medizin II, Zentrum für Medizinische Forschung, Tübingen Ageing and

Tumour Immunology Group, Eberhard-Karls-Universität Tübingen, Tübingen

Russia• Vladimir N. Anisimov, Department of Carcinogenesis and Oncogerontology, N.N. Petrov

Research Institute of Oncology, St.Petersburg


STEM CELL PATENTS: EUROPEAN PATENT LAW AND ETHICS

Proposal acronym StemCellPatents EC contribution (€) 249.257Contract n° LSSB-CT-2004-005251 Instrument SSADuration (starting date) 4 Years (01.01.05) Participants 5

Abstract:

Stem cell research, and embryonic stem cell research in particular, offers the prospect of developing new therapies forserious or life-threatening diseases. But for the potential offered by stem cell research to be realized into therapeuticproducts, industrial or commercial investment is required. At the same time, embryonic stem cell research raises difficultand controverted moral questions which are reflected in the variety of moral perspectives and regulatory regulatoryregimes already adopted or currently being developed in EU member States which vary from total prohibition to qualifiedauthorization in varying forms and degrees. The diversity of legal regimes regulating embryonic stem cell research inEurope together with the subsidiarity principle which devolves competency on legislation concerning ethical questions tomembers States, has created uncertainty as to the legal scope of the "moral exclusion" clause in Article 6 of Directive98/44EC of 6 July 1998 on the legal protection of biotechnological inventions. Clarification on the scope of the Directiveis essential to foster research and investment in Europe whilst ensruring that such research is conducted within clearethical limits which address the concerns of society. The project aims to provide an analysis of the EU patent system, asapplied to biotechnological inventions in general and to embryonic stem cell related technology in particular with a viewto ascertain the legal effect of ethical or legal divergence on European patent law. The multi-faceted nature of thequestion raised requires the combined efforts of experts from different disiplines to contribute to the coordination,analysis and dissemination of knowledge in this area. The multidisciplinary character of the Consortium is intended tobring the required breadth and depth of expertise to bear on the project.

Web site: http://www.nottingham.ac.uk/law/StemCellProject

Participants:

Coordinator

United Kingdom

Dr. Aurora Plomer, The University of Nottingham, School of Law, Nottinghamtel: +44 115 9515717 fax: +44 115 [email protected]

Belgium• Francis Crawley, European Forum for Good Clinical Practice, Brussels

Canada• Bartha Knoppers, Universite de Montreal, Faculty of Law, Montreal (Quebec)

Sweden• Marianne Levin, Stockholm University, Institute for Intellectual Property and Market Law (IFIM),

Stockholm

United Kingdom• John Sinden, ReNeuron Ltd, Head Officer, Guildford, SME


A WORLDWIDE STUDY OF UMBILICAL CORD CELL BANKING

Proposal acronym – EC contribution (€) 13.000Contract n° SAS5-CT-2002-30038 Instrument –Duration (starting date) 5 months (01.10.02) Participants 1

Abstract:

Since a few years a different organisations are active in the banking of umbilical cord cells. Umbilical cord blood containsstem cells which are similar to the cells found in human bone marrow. These cells are now stored for 2 main reasons:either for the benefit of other patients who could benefit from a stem cell transplant or for the individual donor at a laterstage in his or her life (autologous transplantation). The objective of the study is to understand the extent of thesepractices, the way they are organised and their economic impact.

Web site: http://www.ccels.cf.ac.uk/pubs/gunningpaper.html

Participants:

Contractor

United Kingdom

Dr. Jennifer Gunning, Consultant in Bioethisc and Science Affairstel: +44 1225 316629 fax: +44 1225 [email protected]

Commission: Directorate General for Research - Science & Society Directorate - Unit C3 Ethics and Science

Neurectoderm-derived tissues and organs: brain, spine, nerves, sensory organsARTEMIS, EuroHear, EUROSTEMCELL, EVI-GENORET, INTERDEVO, NanoEar, NEURONE, NEUROscreen, NSR, Plurigenes, RESCUE, STEM-HD, STEMS, STEMSTROKE, STROKEMAP, X-ALD.

OBJECTIVES AND METHODOLOGY

ANNEXClassification of projects by tissues, organs and diseases

A given project can appear under several sub-domains, either in organ/tissues, or diseases. For instance, the project MCSCs (Migrating cancer stem cells in breast and colon cancer) will appear in "Ectoderm-derived epithelia", "endoderm-derived organs", and "cancer". Projects not related to any of these domains were classified under "transversal issues".

In the pdf version of the book, this cross-cutting classification is a second way of accessing the projects using the bookmarks, where clickable links give access to the projects listed under this second table of content.

ORGANS & TISSUES

DISEASES

Ectoderm-derived epithelia: skin and annexes, cornea, ectoderm-related exocrine glandsCORNEA ENGINEERING, EPISTEM, EuroCSC, EUROSTEMCELL, MCSCs, SKINTHERAPY, STEPS, THERAPEUSKIN, Ulcer Therapy

Mesoderm-derived tissues and organs: connective tissues, muscles, tendons, fascia, bones, cartilage, fatAUTOBONE, CELLS INTO ORGANS, EPI-VECTOR, EURO-Laminopathies, EuroBoNet, EuroSTEC, EUROSTEMCELL, EXPERTISSUES, GENOSTEM, HIPPOCRATES, MYOAMP, MYOCARDIAL REPAIR, MYORES, NANOBIOCOM, NEWBONE, OsteoCord, SILKBONE, SmartCaP, STEPS, SyntheGeneDelivery

Organs and tissues of mesodermal and composite origin: heart, blood vessels, lymphatic vesselsBIOSYS, CELLS INTO ORGANS, EURO-Laminopathies, EVGN, HeartRepair, INVITROHEART, LYMPHANGIOGENOMICS, MCSCs, MYOCARDIAL REPAIR, SC&CR, VASCUPLUG

Endoderm-derived organs: digestive, respiratory and urogenital tracts, glands and annexesBARP+, BETACELLTHERAPY, CELLS INTO ORGANS, EPI-VECTOR, EUGENE2, EuReGene, EURO-Laminopathies, EuroSTEC, KIDSTEM, LIVEBIOMAT, REGULATORY GENOMICS

Other organs and tissues of composite origin: blood, hematopoeitic organs, immune system organsBARP+, BETACELLTHERAPY, CELLS INTO ORGANS, EPI-VECTOR, EUGENE2, EuReGene, EURO-Laminopathies, EuroSTEC, KIDSTEM, LIVEBIOMAT, REGULATORY GENOMICS

CancersALLOSTEM, Anti-tumor targeting, CONTROL CANCER STEM, E.E.T.-Pipeline, EuroBoNet, EuroCSC, EUROPEAN LEUKEMIANET, EUROPEAN MCL NETWORK, EUROXY, FIRST, GIANT, M3CS-TU TH, MCSCs, MOL CANCER MED, MSCNET, ONCASYM, REGULATORY GENOMICS, SENECA, TUMOR-HOST GENOMICS

Rare diseases (and some less rare heritable diseases)CONSERT, EPISTEM, EURO-Laminopathies, SKINTHERAPY, STEM-HD, SyntheGeneDelivery, THERAPEUSKIN, X-ALD

TRANSVERSAL ISSUES

3G-SCAFF, CARCINOGENOMICS, CellPROM, CLINT, CRYSTAL, Custom-IMD, DNA REPAIR, EMBRYOMICS, EMRS, ESTOOLS, EU hESC registry, EUCOMM, EUROCITS, EuTRACC, FunGenES, imgbchimerashybrids, INDUSTRYVECTORTRAIN, INTHER, INVIVOVECTORTRAIN, MODEST, NEURO, PREDICTOMICS, REPROGENETICS, ReProTect, SIROCCO, StemCellPatents, THE EPIGENOME, TherCord, TRANSCODE, VITROCELLOMICS