Division of work in the Workplan

David Hulmes

Institut de Biologie et Chimie des Protéines, CNRS UMR 5086, Lyon, France

Three-dimensional reconstruction of human corneas by tissue

engineering

Acronym : CORNEA ENGINEERING

Coordinator : D Hulmes, Institut de Biologie et Chimie des Protéines, CNRS UMR 5086, Lyon

European Commission

THE CORNEA

epithelial cells

endothelial cells

stromal cells(keratocytes)

Bowmansmembrane

Descemetsmembrane

extracellular matrix of

collagen fibrils and

proteoglycans

WP 4 : Building the Cell Scaffold

WP 2 : Recombinant

Proteins

WP 3 : Extracellular

Enzymes

WP 5 : Stem Cells

WP 6 : Cell-Matrix Interactions

WP 7 : Tissue

engineering

WP 9 : Functional

Testing

WP 1 : Coordination and Management

WP 10 : Exploitation and Dissemination

WP 8 : Clinical Testing

WORKPACKAGE ORGANISATION

WORKPACKAGES

WPNo Workpackage title L

ead

con

t-ra

ctor

No

WP1 Co-ordination and ProjectManagement 1b 35 0 36

D1D7D20D22

WP2 Recombinant Proteins 1d 180 0 18 D4

WP3 Extracellular Enzymes 13 128 0 18 D5D6

WP4 Building the Cell Scaffold 11 158 6 30 D8D11

WP5 Stem Cells 8 203 0 30D3D12D13

WP6 Cell-Matrix Interactions andBasement Membranes 1c 97 6 30 D14

D15

WP7 Tissue Engineering 1a 149 0 36 D9D16

WP8 Clinical Testing 7 237 6 30 D10

WP9 Functional Testing 2 165 12 36D17D18D19

WP10 Exploitation andDissemination 1b 70 0 36 D2

D21

TOTAL 1412

Per

son

-m

onth

s

Sta

rtm

onth

En

dm

onth

Del

iver

-ab

le N

o

Oth

erp

artn

ers

invo

lved

3

1b,1c,1d,10,11,13

1b,1c,1d,10,11,12,13

1b,1d,5,10,11,14

3,6,7,8

1c,1d,6,11,13

1a,5,6,8,91a,2,3,4,7,8

2,5,6,7,8,9

All partners

One or several partners per workpackage ?

CORNEA ENGINEERING - WORKPLAN

Workpackages MonthNo. Title 0 3 6 9 12 15 18 21 24 27 30 33 361 Co-ordination and

Management2 Recombinant

Proteins3 Extracellular

Enzymes4 Building the Cell

Scaffold5 Stem Cells6 Cell-Matrix

Interactions andBasementMembranes

7 Tissue Engineering8 Clinical Testing9 Functional Testing10 Exploitation and

Dissemination

DELIVERABLES

Deliverable name WP No. Nature

D1 Project presentation 1 1a 1 R PU 3

D4Protocols for production of recombinant proteins

2 1d 180 R PU 18

D5C-proteinases and associated proteins

3 13 84 R PU 18

D6 3 10 44 R PU 18

D7 Mid-term report 1 1b 15 R PU 18

D8Collagen/proteoglycan fibril composites

4 11 79 R PU 24

D9Production of a hemi-cornea

7 1a 75 P CO 24

D2Optimisation of culture ofepithelial cells

5 8 20 R PU 6

Per

son

-m

onth

s

Dis

sem

in-

atio

n le

vel

Del

iver

yD

ate

(mon

th)

Lea

d c

ont-

ract

or N

o

One or several partners per deliverable ?

Oth

erp

artn

ers

invo

lved

-

D3Initial plan for use anddissemmination of knowledge

10 1b 20 R CO 12all

N-proteinases

-

1b,1c,10,11,12,13

1b

all

-

1b,10

1b,6,8,14

Del

No.

David Hulmes

Institut de Biologie et Chimie des Protéines, CNRS UMR 5086, Lyon, France

Hints on project writing

Start early ! (12 months before the deadline)

• Attend a training course on how to write a proposal (e.g. www.hyperion.ie)

• Choose a good project !• Identify a need (consult EC documents and directives

at www.europa.eu.int)• Become an expert evaluator (www.cordis.lu/experts)• Get in touch with national FP6 representatives and

their delegations in Brussels • Arrange a meeting with a Commission officer in an

area related to your project

Corneal grafting (10,000 / year in Europe)

• shortage of donors, unsuitability of tissue (HIV, Creutzfeld-Jacob, Hepatitis C, corrective surgery)

• limitations of artificial keratoprostheses

• 6 million world-wide blinded by infectious diseases of the cornea

WHY RECONSTRUCTED CORNEAS ?

Pharmacotoxicology

• alternatives to animal testing (Draize test)

Building the consortium(at least 6 months before the deadline)

• Define clear and measurable goals • Choose the best people for the job, not just your

friends• Good mix of nationalities (do not exceed the 40 %

rule for any one country) • Complementarity of basic research (different

disciplines), applied research and socioeconomic partners

• Arrange a first meeting of the consortium • Assign clearly defined roles for each partner

GOAL :

• to reconstruct an artificial cornea using recombinant human extracellular matrix proteins and adult stem-cell derived epithelial, stromal and endothelial cells

REQUIREMENTS :

• biocompatibility and stability• optical transparency and refractive properties• mechanical strength

OVERVIEW

THE CONSORTIUM - Countries

France• Institut de Biologie et Chimie des Protéines, CNRS

UMR 5086 Lyon (3 groups)

• Skin Substitutes Laboratory and Corneal Tissue Bank, E. Herriot Hospital, Lyon

• Ophthalmology Department, Hôtel-Dieu, Paris

• Banque Française des Yeux, Paris

• IOLTECH LABORATORIES (SME), La Rochelle

• COLETICA (SME), Lyon

Germany• Universitats-Augenklinik, Hamburg

Israel• Goldschleger Eye Research Institute, Tel Aviv

University

Sweden• Department of Cell and Molecular Biology, University

of Lund

Italy• Laboratory of Tissue Engineering, Fondazione Bana

degli Occhi del Veneto, Mestre Venezia

• Ophthalmology Department, San Raffaele Hospital, Milan

Belgium• Lab. of Connective Tissue Biology, Université de Liège

United Kingdom• Departments of Civil Engineering, Ophthalmology and

Mathematics, University of Dundee

Finland• FIBROGEN EUROPE / University of Oulu

Turkey• Biotechnology Research Unit, Middle East Technical

University, Ankara

THE CONSORTIUM - Expertise

Industrial Partners• IOLTECH LABORATORIES (SME), La

Rochelle, France

• COLETICA (SME), Lyon, France

• FIBROGEN EUROPE / University of Oulu, Finland

Fundamental Research

Institut de Biologie et Chimie des Protéines, CNRS UMR 5086 Lyon, France (3 groups)

Universitats-Augenklinik, Hamburg, Germany

Department of Cell and Molecular Biology, University of Lund, Sweden

Lab. of Connective Tissue Biology, Université de Liège, Belgium

Departments of Civil Engineering, Ophthalmology and Mathematics, University of Dundee, UK

Goldschleger Eye Research Institute, Tel Aviv University, Israel

Biotechnology Research Unit, Middle East Technical University, Ankara, Turkey

Applied Research/ Ophthalmology• Skin Substitutes Laboratory and Corneal

Tissue Bank, E. Herriot Hospital, Lyon, France

• Laboratory of Tissue Engineering, Fondazione Bana degli Occhi del Veneto, Mestre Venezia, Italy

• Ophthalmology Department, San Raffaele Hospital, Milan, Italy

• Ophthalmology Department, Hôtel-Dieu, Paris, France

• Banque Française des Yeux, Paris, France

Partner No. 1a 1b 1c 1d 2 3 4 5 6 8 9 10 11 12 13 14

Partner Short Name

CN

RS-

DR

07

CN

RS-

DR

07

CN

RS-

DR

07

CN

RS-

DR

07

LB

O

BFY

IOL

TE

CH

H

CO

LE

TIC

A

UK

E

HSR

EB

FV

UoD

UL

g

UL

UN

D

FGE

TA

U

ME

TU

Partner Type (A = academic, C =clinical, I = industrial)

A A A A C C I I A A A A A I A A

Management X X X X

Recombinant Proteins X X X X

Collagens X X X

Proteoglycans X

Matrix Enzymes X X X

Matrix Assembly X

Epithelial Stem Cells X

Endothelial Stem Cells X

Keratocytes X

Cell Matrix Interactions X

Tissue Engineering (TE) X X X

Scaffolds for TE X

Mathematical Modelling X

Biomechanics X

Tissue Banking X X X

Corneal Grafting X X

Animal Models X

Keratoprostheses X

EX

PER

TIS

E

Pharmacotoxicology X

COMPLEMENTARITY OF EXPERTISE

C

Writing the proposal(start at least 3 months before

deadline)

• Diagrams• Deliverables and milestones • Cost models and person months • Don’t just concentrate on the science and technology,

other aspects are equally important :• Quality of the consortium• Relevance • Impact • Mobilisation of resources• Management (need for a project manager)

• Gender issues• Ethical issues• Consortium agreement

WP 4 : Building the Cell Scaffold

WP 2 : Recombinant

Proteins

WP 3 : Extracellular

Enzymes

WP 5 : Stem Cells

WP 6 : Cell-Matrix Interactions

WP 7 : Tissue

engineering

WP 9 : Functional

Testing

WP 1 : Coordination and Management

WP 10 : Exploitation and Dissemination

WP 8 : Clinical Testing

WORKPACKAGE ORGANISATION

CORNEA ENGINEERING - WORKPLAN

Workpackages MonthNo. Title 0 3 6 9 12 15 18 21 24 27 30 33 361 Co-ordination and

Management2 Recombinant

Proteins3 Extracellular

Enzymes4 Building the Cell

Scaffold5 Stem Cells6 Cell-Matrix

Interactions andBasementMembranes

7 Tissue Engineering8 Clinical Testing9 Functional Testing10 Exploitation and

Dissemination

DELIVERABLES - for measuring progress

22 deliverables in total, not too many, not too few

Del.no

Deliverable name WP No. Nature

D1 Project presentation 1 1a 1 R PU 3

D4Protocols for production of recombinant proteins

2 1d 180 R PU 18

D5C-proteinases and associated proteins

3 13 84 R PU 18

D6 3 10 44 R PU 18

D7 Mid-term report 1 1b 15 R PU 18

D8Collagen/proteoglycan fibril composites

4 11 79 R PU 24

D9Production of a hemi-cornea

7 1a 75 P CO 24

D2Optimisation of culture ofepithelial cells

5 8 20 R PU 6

Per

son

-m

onth

s

Dis

sem

in-

atio

n le

vel

Del

iver

yD

ate

(mon

th)

Lea

d c

ont-

ract

or N

o

Oth

erp

artn

ers

invo

lved

-

D3Initial plan for use anddissemmination of knowledge

10 1b 20 R CO 12all

N-proteinases

-

1b,1c,10,11,12,13

1b

all

-

1b,10

1b,6,8,14

MILESTONES - key decision points

Milestone Month Objective

1 18 Availability of recombinant extracellular matrix proteins for use inbuilding scaffolds (WP2)

2 18 Identification of key enzymes, variants and associated proteins foruse in building scaffolds (WP3)

3 30 Identification of adult corneal epithelial and endothelial stem cellsources (WP5)

4 30 Protocols for scaffold construction meeting biological, biomechanicaland optical criteria (WP4)

5 30 Identification of optimal conditions for epithelialisation,endothelialisation, stromal and basement membrane assembly (WP6)

6 30 Availability of reconstructed full depth or hemi-corneas (WP7)

7 30 Validation of protocols using limbal-derived corneal epithelial cellsfor the treatment of superficial corneal injury (WP8)

8 36 Validation of reconstructed full-depth or hemi-corneas in animalmodels for use in tissue grafting (WP9)

9 36 Validation of reconstructed full-depth or hemi-corneas for use asalternatives to animal testing for toxicity testing (WP9)

Maximum grant as percentage offull costs (participants applying the

FC or FCF model)

Maximum grant as percentageof additional costs(participants applying the ACFmodel)

RTD activities 50% 100%Demonstration activities 35% 100%Innovation-relatedactivities

50% 100%

Consortium managementactivities

100% (up to a maximumpercentage of 7% of the

Community contribution)

100% (up to a maximumpercentage of 7% of the

Community contribution)

COST MODELS

STRP Project Effort Form

Participant 1.CNRS-DR07

2.APHP-HTD

3.BFY

4.IOLTECH

5.COLETICA

6.UKE

7.HSR

Research/innovation activitiesWP2 Recomb. Proteins 27/61 0/0 0/0 0/0 0/0 0/0 0/0WP3 Extracell. Enzymes 2/45 0/0 0/0 0/0 0/0 0/0 0/0WP4 Cell Scaffold 28/48 0/0 0/0 0/0 1/1 0/0 0/0WP5 Stem Cells 0/0 0/0 9/21 0/0 0/0 20/62 18/30WP6 Cell-Matrix & BM 27/60 0/0 0/0 0/0 0/0 5/16 0/0WP7 Tissue Engineering 30/66 0/0 0/0 0/0 10/20 5/15 0/0WP9 Functional Testing 0/0 12/65 0/0 0/0 10/20 0/5 0/27

TotalResearch/innovation 114/280 12/65 9/21 0/0 21/41 30/98 18/57

Demonstration activities

WP8 Clinical Testing 0/6 0/40 9/21 0/24 0/0 0/0 18/42Total Demonstration 0/6 0/40 0/2 0/24 0/0 0/0 18/42

Management activitiesWP1 Co-ord. Management 12/19 0/1 4/4 0/1 0/1 0/1 0/1WP10 Exploit. Dissemin. 6/14 0/2 2/2 0/12 0/12 0/2 0/2Total Management 18/33 0/3 6/6 0/13 0/13 0/3 0/3

TOTAL ACTIVITIES 132/319 12/108 24/48 0/37 21/54 30/101 36/102

Note : For each partner, two figures are given for person-months (PMs): (1) PM’s for staff whose salaries are to be funded by the project, (2) PMs for all staff to be deployed (salaries funded or not by the project).

Ethics and Standardisation Advisory Panel

Intellectual Property Council

General Assembly

Executive Board

WP 1 WP 2 WP 4WP 3

WP 6 WP 10WP 7 WP 8 WP 9

WP 5

MANAGEMENT STRUCTURE

Evaluation Summary Report for a STREP

Proposal No. : 504017-1 Acronym : CORNEA ENGINEERING

1. Relevance (Threshold 3/5; Weight 1)The project is innovative and ambitious and fits 3.4.4.2 as well as objectives of Priority 1.Correct selection of standardization authorities.

Mark: 4.2

2. Potential impact (Threshold 3/5; Weight 1)Major areas of potential impact that can be an alternative to animal experimentation. It canlead to savings in health care costs and addresses cornea donor shortage. Detailedexploitation/dissemination plan should be provided.

Mark: 4.2

3. S&T excellence (Threshold 4/5; Weight 1)Very clearly defined and focused objectives. Very ambitious project. There is a risk with thescaffolds. A WP on scaffold evaluation (biomechanical, biocompatibility) should be added. Arisk management plan should also be added with alternatives planned.

Mark: 4.5

4. Quality of the consortium (Threshold 3/5; Weight 1)The consortium is high quality, interdisciplinary, well suited, and complementary withexperience in joint work among some partners. There are three SME’s involved.

Mark: 4.2

5. Quality of the management (Threshold 3/5; Weight 1)The plan is adequate for management steering and decision making for the projectknowledge, IPR and innovation related issues. However, the consortium is very large and itcan be problematic, especially with regard to IPR.

Mark: 3.8

6. Mobilisation of the resources (Threshold 3/5; Weight 1)Well planned, coherent project with good mobilization of resources. Travel budgets have tobe discussed.

Mark: 4.3

Overall remarks (Threshold 21/30)Recommended budget cut of 20%.

Total score:

25.2

Has the proposal passed all evaluation thresholds? YesDoes this proposal have ethical issues that need further attention? Yes