University of California, Davis

University of California, Los Angeles

University of California, San Diego

University of California, Santa Barbara

University of California, Santa Cruz

Ohio State University

University of Tuebingen

Zhejiang University

University of Science and Technology, Beijing

Indian Institute of Science

Nanyang Technological University

Collaboration and Invited Universities

15(Sun) and 16(Mon) March 2009Hotel Metropolitan Edmont, Banri(2F)

17(Tue) March 2009 Round Table Discussion and Campus Tour at Noda

Biological Science and Technology

3rd Tokyo University of ScienceInternational Collaboration Workshop

(TUS-ICW)Joint Hosting:Division of Chemical Biology etc, Research Institute for Science and Technology

Workshop Program

HotelMetropolitan Edmont

InternationalExchange Office

Iidab

ashi

Sta. JR

Tokyo Universityof Science

Topics

Tokyo University of ScienceCenter for Promotion of Internationalization

Workshop Secretariat

International Exchange Office1-3 Kagurazaka, Shinjuku-ku, Tokyo, 162-8601 JAPANPhone : +81-(0)3-5228-8726 FAX : +81-(0)3-5228-8727HP : http://www.tus.ac.jp/enE-mail : intlexchg@admin.tus.ac.jp

Workshop Place

Hotel Metropolitan Edmont, Banri(2F)3-10-8 Iidabashi, Chiyoda-ku, Tokyo, 102-8130 JAPANPhone: +81-(0)3-3237-1111

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3rd Tokyo University of Science International Collaboration Workshop

(3rd TUS-ICW)

Topics: Biological Science and Technology

Joint Hosting: Division of Chemical Biology Research, etc. Research Institute for Science and Technology

Date: March 15 and 16, Workshop Place: Hotel Metropolitan Edmont, Tokyo Date: March 17, Noda Campus / Laboratories Tours and Round Table Discussion Place: TUS Noda Campus

Programs

Content

Organization ..........................................................................................................................2 Workshop Program ................................................................................................................4 Abstracts ................................................................................................................................9 Titles of Posters at Poster Session ......................................................................................38

Supported by the MEXT Program for Promotion of Internationalization, Tokyo University of Science

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Organization Host University: Tokyo University of Science Collaboration and Invited Universities: University of California, Davis, USA University of California, Santa Cruz, USA University of California, Santa Barbara, USA University of California, San Diego, USA University of California, Los Angels, USA Ohio State University, USA University of Tuebingen, Germany Zhejiang University, PR China University of Science and Technology, Beijing, PR China Indian Institute of Science, India Nanyang Technological University, Singapore International Collaboration Program Committee: Iwao Hashimoto (Chair, Dean of Faculty of Science) Yoshihiro Maruyama (Professor, Liberal Arts Program) Shizuo Miyajima (Professor, Department of Mathematics) Hiroshi Yabe (Professor, Department of Mathematical Information Science) Yoshimi Egawa (Professor, Department of Mathematical Information Science) Kazuyuki Watanabe (Professor, Department of Physics) Yukihiro Ishii (Professor, Department of Applied Physics) Tomohiko Saitoh (Associate Professor, Department of Applied Physics) Kazuo Miyamura (Professor, Department of Chemistry) Takeo Furukawa (Professor, Department of Chemistry) Hirofumi Yajima (Professor, Department of Applied Chemistry) Fumio Sugawara (Professor, Department of Applied Biological Science) Masahiko Ikekita (Professor, Department of Applied Biological Science) Kiyoichiro Motoya (Professor, Department of Physics) Hideyuki Suzuki (Professor, Department of Physics) Shigeru Ito (Professor, Department of Pure and Applied Chemistry) Hideki Sakai (Associate Professor, Department of Pure and Applied Chemistry) Yasuo Nakatani (Associate Professor, School of Management) Shinya Nogami (Associate Professor, School of Management Tadanori Mizoguchi (Executive Director, Center for Promotion of Internationalization) Cooperated by Robert Powell (Professor, Department of Chemical Engineering and Materials Sciences, University of California, Davis)

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Warren Pickett (Professor, Department of Physics, University of California, Davis) Yayoi Takamura (Assistant Professor, Department of Chemical Engineering and Materials Science, University of California, Davis) David Belanger (Professor, Department of Physics, University of California, Santa Cruz) Joseph Konopelski (Professor, Department of Chemistry, University of California, Santa Cruz) Dieter Wanner (Associate Provost, Office of International Affairs, Ohio State University) Matthew Platz (Dean, College of Mathematical and Physical Sciences, Ohio State University) Loy Lytle (Dean, Extended Learning Service, University of California, Santa Barbara) Matthew Tirrell (Dean, College of Engineering, University of California, Santa Barbara) David Unruh (Assistant Provost, Academic Program Development, University of California, Los Angels) David Lundberg (Director, California Nano-System Institute, University of California, Los Angels)

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Workshop Program March 15 (Sun): Subtopics: Biochemistry and Chemical Biology

9:00 – 9:05 Welcome by President Shin Takeuchi 9:05 – 9:15 TUS International Collaboration Programs, Tadanori Mizoguchi, Executive Director,

Center for Promotion of Internationalization 9:15 – 9:30 Biology Research and Education at TUS, Masahiko Ikekita, Professor and a member

of Board of Governance

9:30 – 9:50 Yujiro Hayashi, Professor, Department of Industrial Chemistry, TUS “Synthesis of small organic molecules with strong biological activity for the

chemical biology” 9:50 – 10:20 Thomas R.R. Pettus, Professor, Department of Chemistry, UC Santa

Barbara “Synthesis and Evaluation of Small Molecules as Telomerase Inhibitors: an

academician's perspective on improving compound efficacy for a monster of an enzyme”

10:20 – 10:50 Joe Konopelski, Professor, Department of Chemistry, UC Santa Cruz “Heterocycles in Natural Product Synthesis” 10:50 – 11:10 Coffee Break

11:10 – 11:40 Yoshihisa Kobayashi, Assistant Professor, Department of Chemistry and

Biochemistry, UC San Diego “Heterocycles in Natural Product Synthesis” 11:40 – 12:10 Phil Crews, Professor, Department of Chemistry, UC Santa Cruz “Discovery of Marine Natural Products as Therapeutic Leads — Some

Effective Paradigms and Significant Outcomes” 12:10 – 12:40 Bradley Moore, Professor, Scripps Institution of Oceanography and Skaggs

School of Pharmaceutical Sciences, UC San Diego “Genomic Exploration and Exploitation of Marine Bacteria for Natural

Products” 12:40 – 14:00 Lunch

14:00 – 14:20 Fumio Sugawara, Professor, Department of Applied Biological Science,

TUS “New Screening Methods for Protein-Protein Interaction Inhibitors Based on ERET and Phage Display”

14:20 – 14:50 Yunfeng Lu, Professor, Department of Chemical and Biomolecular Engineering, UCLA

“A Novel Protein Delivery Platform Based on Single Protein Nanocapsules” 14:50 – 15:20 Kengo Morohashi, Researcher, Department of Plant Cellular and

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Molecular Biology, Ohio State University “Chemical biology approach highlights a critical role of a novel cyclosporin

A binding protein, CSABP, in hepatitis C virus replication” 15:20 – 15:50 Robert Powell, Department of Chemical Engineering and Materials

Science, UC Davis “Experimental Methods for the Study of Multiphase Materials” 15:50 – 16:10 Coffee Break 16:10 – 16:30 Isamu Shiina, Professor, Department of Applied Chemistry, TUS “Recent Progress in the Synthesis of Biologically Active Compounds Using

Dehydration Condensation Reactions” 16:30 – 17:00 Yi Tang, Associate Professor, Department of Chemical and Biomolecular

Engineering, UCLA “Engineering E. coli to Produce A Blockbuster Drug” 17:00 – 17:30 Shang-Tian Yang, Professor, Department of Chemical and Biomolecular

Engineering, Ohio State University “Microbioreactor Arrays for High-Throughput Screening (HTS) in Drug

Discovery and Bioprocess Development” 17:30 – 18:00 Lee Pooi See, School of Materials Science and Engineering, Nanyang Technological

University “DNA Sensing by Field Effect Transistors” 18:45 Reception

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March 16 (Mon): Subtopics: Molecular Biological Science and Technology 9:00 – 9:20 Kenji Matsuno, Professor, Department of Biological Science and Technology,

TUS “A Drosophila model of peroxisome disease revealed an essential role of

peroxisome in male-specific germ cell maturation” 9:20 – 9:50 Joel Rothman, Professor, Department of Molecular, Cellular and

Developmental Biology, UC Santa Barbara “ Regulation of stem cell differentiation in C. elegans.” 9:50 – 10:20 Kazuhiro Shiozaki, Professor, Department of Microbiology, UC Davis “Fission yeast as a genetic model to unravel cellular signaling pathways in

diseases” 10:20 – 10:50 Sandhya Visweswariah, Professor, Molecular Reproduction Development

and Genetics (MRDG), Indian Institute of Science “An evolutionarily conserved metallophosphodiesterase: bacteria, flies and

the human WAGR syndrome” 10:50 – 11:20 Yuhong Xu, Professor, Zhejiang California International NanoSystems

Institute (ZCNI), Zhejiang University “Self-assembled lipid/DNA nanoparticles for pMDI aerosol delivery of

genes to the lung” 11:30 – 14:00 Poster Session Core Time (Lunch provided) (Posted from 10:00 AM to 4:00 PM) 14:00 – 14:30 S. Benjamin Hua, Professor, Zhejiang California International

NanoSystems Institute (ZCNI), Zhejiang University "Application of Two-Hybrid System in Antibody Discovery" 14:30 – 15:00 Siddhartha Sarma, Professor, Molecular Biophysics Unit (MBU), Indian

Institute of Science “Structural studies of Peptide Toxins from Indian Marine Cone Snails” 15:00 – 15:30 Shi GuoQing, University of Science and Technology, Beijing “Cellular proteasome is a molecular target of organotin compounds.”

15:30 – 15:50 Coffee Break

15:50 – 16:10 Kazuyuki Kuchitsu, Dept. of Applied Biological Science, TUS

“Roles of Ca2+ and reactive oxygen species in signaling network regulating innate immunity, programmed cell death and development in plants”

16:10 – 16:40 Anne Britt, Professor, Department of Plant Biology, UC Davis “The NAC domain transcription factor Suppressor of Gamma Response 1

(Sog1) governs programmed response to DNA damage”

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16:40 – 17:10 Dierk Wanke, Center for Plant Molecular Biology, University of Tuebingen “The Promoter Code: Insights into eukaryote transcription from plant

transcription factors and their DNA-motif companions” 17:10 – 17:40 Kentaro Inoue, Associate Professor, Department of Plant Sciences CA&ES,

UC Davis “Evolutionary conserved essential proteins in the chloroplast outer

membrane - from endosymbiosis to membrane biogenesis” 17:40 – 18:10 Allen Van Deynze, Professional Researcher, Department of Plant Sciences,

UC Davis “The Application of Biotechnology and Genomics to Plant Breeding” 18:15 Adjourn 19:00 Dinner (Planned)

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March 17 (Tue) Noda Campus Lab Tour and Round Table Discussion 9:30 Leave the hotel by bus for TUS Noda Campus 10:30 – 12:00 Round Table Discussion 12:00 – 13:00 Lunch 13:00 – 15:30 Laboratories Tour

@ Department of. Applied Biological Science and others @ Research Institute of Biological Science, @ Drug Delivery System Research Center, @ Genome and Drug Research Center, @ Nano Particle Health Science Research Center, etc. 16:00 Leave Noda Campus

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Abstracts

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Sunday 15 March, 9:30-9:50

Synthesis of small organic molecules with strong biological activity for the chemical biology

Yujiro Hayashi

Department of Industrial Chemistry, Faculty of Engeering, Tokyo University of Science

Our group has been interested in the synthesis of natural products with strong biological activity for the last ten years. In this presentation, I would like to focus on three small organic molecules such as epolactaene, cytotrienin A, and tamiflu. Epolactaene is a microbial metabolite, promoting neurite outgrowth and arresting the cell cycle at the G1 phase. We have accomplished the first asymmetric total synthesis. By the collaborative work with biologists, the target protein was determined. Cytotrienin A, a microbial antitumor secondary metabolite, exhibits potent apoptosis-inducing activity on HL–60 cells, with an ED50 value of 7.7 nM. We synthesized this natural product for the first time using organocatalyst-mediated asymmetric reactions, developed in our group, as key steps. Oseltamivir phosphate (tamiflu) is a neuraminidase inhibitor used in the treatment of both type A and type B human influenza. Recently we have accomplished the high-yielding synthesis of this important drug via three “one-pot” reactions.

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Sunday 15 March, 9:50-10:20

Synthesis and Evaluation of Arylspiroketals as Telomerase Inhibitors: an academician's perspective on improving compound efficacy for a monster of an enzyme

Thomas R. R. Pettus

Department of Chemistry and Biochemisty

University of California, Santa Barbara

Telomerase circumvents nature’s aging clock. 20-150 Bases on ss-telomeric repeat are lost with cell each division because of a replication problem. When the telomere becomes too short, the cell undergoes senescence arrest and/or apoptosis. While absent from most somatic cells, telomerase is found in of 95% of cancer cells to prevent senescence arrest and/or apoptosis and to ensure the immortalization of the cancer cells. Hence, telomerase is a validated selective non-cytotoxic anti-cancer target suitable for drug development. However, despite these facts, inhibitors of only simplest aspects of the telomere elongation cycle are currently in clinical development. We will present the known landscape of small molecule scaffolds putatively reported to inhibit telomerase, and discuss the shortcomings of the current assays in providing accurate SAR data. We will also present improved assays and our synthetic studies aimed at the arylspiroketal β-rubromycin along with the identification the anti-telomerase pharmacophores and auxophores within this natural product.

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Sunday 15 March, 10:20-10:50

Hererocycles in Natural Product Synthesis

Joseph P. Konopelski

Department of Chemistry and Biochemistry University of California, Santa Cruz

For many years our research program has been engaged in various aspects of heterocyclic chemistry as it pertains to the synthesis of biological interesting molecules. If time permits, this presentation will highlight our work on three different projects. One project involves a collaborative effort to understand the detailed mechanism of cytochrome c oxidase, the mitochondrial enzyme responsible for the reduction of dioxygen to water. This project has involved the preparation of the unusual side chain coupled peptide system of the enzyme active site. Another project is directed at the total synthesis of the marine natural products cyclocinamide A and B, cyclic peptides comprised of both α- andβ- amino acids. The third project involves a heretofore undiscovered route to β-lactam structures directly from α-amino acids.

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Sunday 15 March, 11:10-11:40

Heterocycles in Natural Product Synthesis

Yoshihisa Kobayashi

Department of Chemistry and Biochemistry University of California, San Diego

The presentation will cover the recent progress on natural product synthesis by using novel reagents and methodologies related to unique features of nitrogen-containing heterocycles. The development of a new convertible isocyanide, indole-isocyanide, for ready access to pyroglutamic acids via an N-acylindole culminated in the formal total synthesis of the proteasome inhibitor omuralide featuring a stereocontrolled Ugi reaction. Indole-Isocyanide was named after the facilitation of hydrolysis of the resulting 2-(2,2-dimethoxyethyl) anilide by Ugi/(Passerini) multi component condensation reaction, via N-acylindole. A series of biologically intriguing pyroglutamic acids were synthesized in an unprotected form by employing the isocyanide and ammonium acetate in the Ugi 4-center 3-component reaction of gamma-ketoacids.

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Sunday 15 March, 11:40-12:10

Discovery of Marine Natural Products as Therapeutic Leads — Some Effective Paradigms and Significant Outcomes

Phillip Crews

Department of Chemistry and Biochemistry,

University of California, Santa Cruz, CA 95064 E-mail: phil@chemistry.ucsc.edu

Web: www.chemistry.ucsc.edu/mnpr/

The marine natural products program begun at UC Santa Cruz (UCSC) in the early 1970’s has a rich history and continued promise for future significant discoveries. To date, almost 900 molecular structures have been established by the UCSC group from the study of marine invertebrates, especially sponges and marine-dervied fungi, and these continue to captivate the interests of research groups throughout the world. During the talk I will amplify on: (1) new scaffolds being explored for anti-cancer therapeutic lead development, (2) the continuing challenges to obtain sponge-derived compounds seemingly biosynthesized by microbial associants, and (3) the potential and challenges associated with mining complex mixtures obtained from culture of marine-derived fungi.

The introductory discussions will highlight examples from our past discovery of compounds that continue to situmlate much additional research. The sponge-derived bengamides have been a focus of highly collaborative research that spanned some twenty years and culminated in the advancement of a synthetic derivative (NVP-LAF389) into a phase-I anticancer clinical trial. The pederin analog, psymberin discovered in 2004 from Psammocinia, is of continuing interest owing to its potency against cancer cells, its fascinating stereo structural features, and its interesting biosynthetic makeup. We have dealt with sponge-derived polyketide macrolides of the fijianolide family as selective cytotoxins. These compounds have been the subject of basic and preclinical studies; the trials and tribulations encountered along the way provide some interesting lessons. Current unpublished research on bioactive constitutents from various sponge families will be discussed while touching on some structure elucidation challenges. Only limited understanding has been achieved on the potential of marine-derived fungi as a source of inspirational natural products. At the end of 2005, there were less than 400 such biosynthetic products described in the literature from this source versus thousands of small molecules known from marine invertebrates and algae. We continue to find an exciting array of structural classes from our mining of the current and expanding library of fungi. Several examples will be presented including an update on polypeptides and other biosynthetic products. There will also be a moment to consider future prospects. Investigations on marine microorganisms will continue to grow and should provide rewarding outcomes. Especially worthwhile should be the further study of the sponge-derived bacterial communities. We have

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just begun to explore one aspect of this subject and the current focus is on marine-derived myxobactera. Absolutely intriguing are highly cited observations of parallel structures from terrestrial myxobactera and marine sponges. At the top of our list are (a) jasplakinolide (Sponge, Jaspis splendens and Auletta constricta) vs. chondramide A (mycobacteria, Chondromyces crocatus), (b) latrunculin A (Sponge, Cacospongia mycofijiensis and Negombata magnifica) vs. epothilone B (mycobacteria, Sorangium celullosum), and (c) Bengamide E (Sponge, Jaspis coriacea) vs. bengamide E analogues (mycobacteria, Mycoccus virescens).

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Sunday 15 March, 12:10-12:40

Genomic Exploration and Exploitation of Marine Bacteria for Natural Products

Bradley S. Moore

Scripps Institution of Oceanography and the Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA 92093

Email: bsmoore@ucsd.edu Web: http://moorelab.ucsd.edu

Marine actinomycetes belonging to the genus Salinispora have proven to be a rich source of novel secondary metabolites including one compound (salinosporamide A) that is currently in clinical trials for the treatment of cancer. Despite extensive fermentation studies of S. tropica and S. arenicola, recent genome sequencing has revealed an abundance of novel biosynthetic gene clusters in both taxa whose products have yet to be discovered.1-2 This new information provides clear evidence that even these well-studied environmental bacteria continue to represent an important resource for natural product discovery. This presentation will focus on the genomic mining of new chemical entities from Salinispora and the extension of its biosynthetic capacity to small molecules through genetic engineering of established pathways.3-6 1. D. W. Udwary, L. Zeigler, R. Asolkar, V. Singan, A. Lapidus, W. Fenical, P. R. Jensen, and

B. S. Moore, “Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica”, Proc. Natl. Acad. Sci. USA, 104, 10376-10381 (2007).

2. K. Penn, C. Jenkins, M. Nett, D. W. Udwary, E. A. Gontang, R. P. McGlinchey, B. Foster, A. Lapidus, S. Podell, E. Allen, B. S. Moore, and P. R. Jensen, “Genomic islands predict functional adaptation in marine Actinobacteria”, submitted.

3. A. S. Eustáquio and B. S. Moore, “Mutasynthesis of fluorosalinosporamide, a potent and reversible inhibitor of the proteasome”, Angew. Chem. Int. Ed. Engl., 47, 3936-3938 (2008).

4. R. P. McGlinchey, M. Nett, and B. S. Moore, “Unraveling the biosynthesis of the sporolide cyclohexenone building block”, J. Am. Chem. Soc., 130, 2406-2407 (2008).

5. A. Schultz, D.-C. Oh, J. R. Carney, R. T. Williamson, D. W. Udwary, P. R. Jensen, S. J. Gould, W. Fenical, and B. S. Moore, “Biosynthesis and structures of cyclomarins and cyclomarazines, prenylated cyclic peptides of marine actinobacterial origin”, J. Am. Chem. Soc., 130, 4507-4516 (2008).

6. R. P. McGlinchey, M. Nett, A. S. Eustáquio, R. N. Asolkar, W. Fenical, and B. S. Moore, “Engineered biosynthesis of antiprotealide and other unnatural salinosporamide proteasome inhibitors”, J. Am. Chem. Soc., 130, 7822-7823 (2008).

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Sunday 15 March, 14:00-14:20

New Screening Methods for Protein-Protein Interaction Inhibitors Based on ERET and Phage Display

Fumio Sugawara

Department of Applied Biological Science

Tokyo University of Science It is currently of great interests to identify binding proteins that interact with small molecules and also protein-protein interactions in which these associations are studied from the perspective of biochemistry, signal transduction and networks. The interactions between proteins are important for many biological functions. For example, signals from the exterior of a cell are mediated to the inside of that cell by protein-protein interactions of the signaling molecules. This process, called signal transduction, plays a fundamental role in many biological processes and in many diseases (e.g. cancer). The information will help us to understand mammalian biochemical processes and possibly to accelerate the development of novel pharmaceutical and agricultural agents. There are a multitude of methods to detect them. Each of the approaches has its own strengths and weaknesses, especially with regard to the sensitivity and specificity of the method. For example, Co-immunoprecipitation and its common variation, pull-down assay are considered to be a standard assay in laboratory today. However, the methods often have notorious high false-positive rates such as yeast two-hybrid screen which investigates the interaction between artificial fusion proteins inside the nucleus of yeast. Or methods are highly expensive such as surface plasmon resonance to measure protein-protein interaction or chemical cross-linking followed by high mass MALDI mass spectrometry. Here we would like to present new methods for the screening for protein-protein interaction inhibitors; 1) one is essentially applied by FRET (fluorescence resonance energy transfer) e.g. Tsc1/Tsc2 interaction associated with insulin signaling; 2) another is developed from T7 phage display in which a protein expressed with either GST of biotin tagged was immobilized on well-plate and its counterpart was displayed on phage particles, e.g. p53-MDM2 and HPV E7-human pRB interactions.

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Sunday 15 March, 14:20-14:50

A Novel Protein Delivery Platform Based on Single Protein Nanocapsules

Yunfeng Lu

Department of Chemical and Biomolecular Engineering, University of California at Los Angeles, Los Angeles, CA 90095, USA

Proteins, the essential parts of organisms, participate in every metabolic process within cells. Most human diseases are somehow related to the malfunctioning of particular proteins systematically or locally. In this context, protein therapy, which uses proteins with defined structure and well-known biological effect, can be considered as the most direct and safe way for treatment of such diseases. Over the last several decades, recombinant DNA technology and the advances in proteomics paved the way for development of protein therapy by providing a facile method to prepare pharmaceutical proteins. However, broad applications of the protein therapy are still limited by several substantial technical barriers, such as low efficiency of intracellular delivery and poor stability of delivered proteins against proteases. Herein, we report a novel delivery platform based on a nanoscale protein-polymer core-shell architecture. The modified enzymes are highly stable with high cell-permeability and activity both in vitro and in vivo, rendering it a promising potential for therapeutic applications.

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Sunday 15 March, 14:50-15:20

Chemical biology approach highlights a critical role of a novel cyclosporin A binding protein, CSABP, in hepatitis C virus replication

Kengo Morohashi

Department of Plant Cellular and Molecular Biology

Ohio State University Cyclosporin A (CsA) is well known as an immunosuppressive drug useful for allogeneic transplantation. The immunosuppressive mechanism is widely believed to include CsA binding to its primary cytoplasmic receptor cyclophilin (CyP). Surprisingly it has been reported recently that CsA inhibits hepatitis C virus (HCV) genome replication, and CyPB, which is one of CyP family, is involved in CsA-mediated inhibition. Despite CyPB promotes HCV replication, the whole mode of action of CsA against HCV remains unknown. Here we report a chemical biology approach that elucidates novel aspects of HCV replication. We investigated the cellular target molecule of CsA using phage display screening. This protein, named CsA binding protein (CSABP), possessed RNA-dependent ATPase activity that was negated by treatment with CsA. CSABP formed a complex with HCV-derived RNA polymerase NS5B and host-derived CyP in vitro and in vivo. The downregulation and upregulation of CSABP in the cells resulted in decrease and increase of HCV genome replication, respectively, suggesting CSABP plays a critical role with NS5B-CyPB complex in HCV replication. Interestingly, CSABP expression was induced by TNF-alpha, which is induced by inflammation. Considering HCV infection causes liver inflammation, CSABP might work in part of a positive feedback machinery during HCV propagation. Our chemical biology approach shed light on the biological diversity brought about by the action of a compound and could provide further insights into the mechanism of cellular physiology.

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Sunday 15 March, 15:20-15:50

Experimental Methods for the Study of Multiphase Materials

Robert L. Powell

Department of Chemical Engineering and Materials Science University of California, Davis, CA 95616

This talk will review experimental techniques for studying the dynamics of multiphase fluids. The systems that we consider consist of either a solid particle or a liquid drop suspended in a continuous fluid. A core requirement is the ability to work with concentrated opaque systems, which allows working with a wide range of model multiphase fluids as well as with fluids found in real processes. The technique that has perhaps received the most attention is magnetic resonance imaging (MRI). This is essentially the same technique that is employed in medical applications. For studies of multiphase systems, a variety of experiments has been performed. The most widely reported are flow imaging, concentration mapping and diffusivity measurements. Ultrasonics is used for flow imaging and is a lower cost technology than MRI. Over the last decade it has also become an important tool for flow imaging. It is able to make accurate measurements of one and two components of velocity. Ultrasonic Pulsed Doppler Velocimetry (UPDV), the standard velocity imaging technique, can be used for systems of practical interest. Other techniques will be discussed such as X-radiography, neutron tomography and electrical Iimpedance tomography can be used to measure density differences in multiphase systems and hence concentration profiles.

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Sunday 15 March, 16:10-16:30

Recent Progress in the Synthesis of Biologically Active Compounds Using Dehydration Condensation Reactions

Isamu Shiina

Department of Applied Chemistry

Tokyo University of Science We have developed a very effective dehydration condensation reaction promoted by substituted benzoic anhydrides and nucleophilic catalysts. Various macrocyclic antibiotics are effectively prepared from free w-hydroxycarboxylic acids by the combined use of 2-methyl-6-nitrobenzoic anhydride (MNBA) with DAMP or DMAPO under mild reaction conditions. This powerful method is applicable to the syntheses of highly strained cyclic compounds such as medium-sized ring lactones since the reaction rate is very fast enough to produce the monomeric compounds preferentially. Remarkable efficiency of the coupling reaction promoted by the substituted benzoic anhydrides has already been shown in the syntheses of a lot of biologically active compounds. Examples of the successful application for the preparation of useful molecules via this novel method will be presented as listed below.

(1) Production of Macrocyclic Antibiotics Using MNBA Lactonization, (2) Preparation of the Probe Molecules via the Formation of Ester Linkage, (3) Peptide Coupling Reaction without Loss of the Chirality Catalyzed by DMAPO, (4) Production of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Their Esters via

Asymmetric Dehydration Condensation.

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Sunday 15 March, 16:30-17:00

Engineering E. coli to Produce A Blockbuster Drug

Yi Tang

Department of Chemical & Biomolecular Engineering University of California, Los Angeles

Simvastatin is a semisynthetic derivative of the fungal polyketide lovastatin and is an important drug for lowering the cholesterol levels in adults. We have developed an one-step, whole cell biocatalytic process for the synthesis of simvastatin from monacolin J. Using an Escherichia coli strain overexpressing the previously discovered acyltransferase, LovD , we were able to achieve >99% conversion of monacolin J to simvastatin without the use of any chemical protection steps. The key finding was a membrane permeable substrate, alpha-dimethylbutyryl-S-methyl-mercaptopropionate (DMB-S-MMP), that was efficiently utilized by LovD as the acyl donor. The process was scaled up for gram-scale synthesis of simvastatin. We also demonstrated that simvastatin synthesized via this method can be readily purified from the fermentation broth with >90% recovery and >98% purity as determined by HPLC. Bioconversion using high cell density, fed-batch fermentation was also examined. The whole cell biocatalysis can therefore be an attractive alternative to the current, multistep semisynthetic transformations.

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Sunday 15 March, 17:00-17:30

Microbioreactor Arrays for High-Throughput Screening (HTS) in Drug Discovery and Bioprocess Development

Shang-Tian Yang

Department of Chemical and Biomolecular Engineering

The Ohio State University 140 West 19th Avenue, Columbus, OH 43210 Phone: 1-614-292-6611; Fax: 1-614-292-3769

Email: yang.15@osu.edu Abstract We have developed fluorescence-based live 3D cell cultures in microwell plates and microfluidic biochips for high-throughput cytotoxicity assay and drug screening using EGFP-expressing cells. Drug responses of the cells can be monitored in real time and noninvasively. The microbioreactor arrays can also be used for medium optimization and cell culture process development. This is the first cell-based high-throughput system in 3D that can more reliably mimic in vivo environment. The microbioreactor arrays will have wide applications in drug discovery, cell culture process development, and tissue engineering. This presentation will outline the principles and methods used in this 3D HTS system and provide several application examples (cytotoxicity assay, drug efficacy study, and antibody production process optimization).

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Sunday 15 March, 17:30-18:00

DNA Sensing by Field Effect Transistors

Pooi See Lee

School of Materials Science and Engineering Nanyang Technological University, Singapore

Deoxyribonucleic acid (DNA) hybridized biosensors are of interest for fast detection for genetic testing, biological warfare and environmental testing. There are current efforts on highly sensitive electronic detection of biomolecules such as antibodies and label free detection of DNA hybridization using carbon nanotube network field effect transistors (CNNFETs) or single crystalline nanowire field effect transistors. In this work, we study the DNA sensing characteristics using CNNFETs by monitoring the electrical responses upon immobilization with a DNA probe and the enhancement in sensitivity using a reduction-oxidation sensitive intercalator. Changes in signal upon hybridization with DNA analytes, and intercalation with N,N’-bis(3-propylimidazole)-1,4,5,8-napthalene diimde modified with Os(2,2’-bipyridine)2Cl+ pendants have been detected. Immobilization of CNNFETs by single stranded DNA molecules demonstrate the selective sensing of its complementary and single-base mismatched DNA. Specific binding between hybridized DNA and intercalators shows further sensitivity enhancement upon subsequent intercalation. Channel dependent as opposed to contact modulation are the contrasting mechanisms for the electrical detection of DNA hydridization. We proceed to clarify the dominant factor with a junction capping or junction blocking study. We obtained barrier height data providing direct evidence correlating electrode-single wall carbon nanotube energy level alignment with DNA immobilization and hybridization, which suggests the sensing mechanism is through the charge density modification near the electrode-nanotube junctions. The result enables better and alternate sensor design which exploits the pronounced interaction between analytes and electrode-nanotube junctions.

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Monday 16 March, 9:00-9:20 A Drosophila model of peroxisome disease revealed an essential role of peroxisome

in male-specific germ cell maturation

Minoru Nakayama, Takayuki Okuda, Nao Fujisawa, and Kenji Matsuno

Genome and Drug Research Center, Research Institute of Science and technology, Tokyo University of Science

The peroxisome biogenesis disorders (PBDs) are neurodegenerative, multiorgan dysfunction, and currently incurable disorders that result from defective biogenesis of peroxisomes. Although genetic defects responsible for PBDs has been identified, lack of understanding about the pathogenesis of PBDs prevents us form developing effective treatment. Here, to understand defects caused by absence of peroxisoms, we developed a Drosophila model for PBDs, in which Pex16 gene was disrupted. Peroxisomes are generated by two pathways, “grow and fission” or “de novo biogenesis”. Pex16 gene is required for peroxisome de novo biogenesis in yeast and mammals. Drosophila Pex16 mutants showed loss of peroxisomes and phenotypes reminiscent of PBDs symptoms, including neuronal degeneration, motility defects, and shortened life-span. Furthermore, Pex16 mutants showed male-specific sterility that resulted from deficiency of spermatogenesis. Although mild forms of PBDs show severe spermatogenesis defects, roles of peroxisome in spermatogenesis has not been addressed. Spermatocytes in the testes of Pex16 were degenerated during spermatocyte growth stage preceding meiosis. We found that peroxisomes were required for the normal sperm production in somatic cyst cells that were analogous to mammalian sertoli cells. Finally, up-regulation of “grow and fission” for peroxisome proliferation by genetic modification or drug partly restore the lacking of peroxisome in Pex16 homozygote, suggesting that this could be a therapeutic target of PBDs associated with defects in peroxisome de novo synthesis.

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Monday 16 March, 9:20-9:50

Regulation of stem cell differentiation in C. elegans.

Joel H. Rothman,

Department of MCD Biology, University of California, Santa Barbara, CA 93106 USA.

Stem cells can give rise to many differentiated cell types and yet maintain their multipotential condition by self-renewal. Though much progress has been made, the molecular processes that promote “stemness” and their mechanisms of action are not well-understood. What mechanisms allow undifferentiated cells to remain multipotential, i.e., capable of becoming programmed to many different cell fates, but subsequently cause them to become committed to particular pathways of differentiation? We are investigating the mechanisms that restrict the developmental transition from specification to differentiation and the switches that drive cells from a proliferative state in the stem cell “niche” into a pathway of differentiation, using the model experimental animal C. elegans. By functional genomics (RNAi-based) screens, we have identified genes that act to prevent cells from becoming reprogrammed to novel differentiated cell types in embryonic and germline cells. These studies have revealed that chromatin remodeling factors, cell-cell communication, and cell type-specific transcription factors function in regulating the competency of cells to be reprogrammed into different cell types. We have also found that a network of micro RNAs (miRNAs) participate in the regulation of stem cell identity and self-renewal. These findings may lead to methods for generating new stem cell types.

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Monday 16 March, 9:50-10:20

Fission yeast as a genetic model to unravel signaling pathways in diseases

Kaz Shiozaki

Department of Microbiology, University of California, Davis, California, USA

The long-term objective of our research is to understand at a molecular level how cells perceive and respond to diverse stress by elucidating the structure and function of intracellular stress-signaling pathways. Our studies are being carried out with the fission yeast Schizosaccharomyces pombe. This organism has served as an outstanding model system for studying basic cellular functions conserved among eukaryotes. In diverse eukaryotic species, mitogen-activated protein kinase (MAPK) cascades are utilized in sensing and integrating various stress signals to induce protective responses. We have demonstrated that the Spc1 MAPK pathway in S. pombe is remarkably homologous to the mammalian SAPK (stress-activated protein kinase) pathways, which determine cancer cells’ response to chemotherapy/radiotherapy as well as inflammatory responses in diseases such as asthma, arthritis and bacterial infection. In both mammals and fission yeast, the stress MAPK pathways have important roles in linking growth controls with environmental signals. Our current research interests are (1) to understand how cells sense and transmit diverse stress stimuli, including osmostress, heat shock and oxidative stress to activate Spc1 MAPK; (2) to uncover how the stress MAPK pathway interacts with signaling pathways involving the TOR (Target Of Rapamycin) protein kinase. The TOR kinase is highly conserved from yeast to human and regulates cell proliferation/metabolism in response to environmental cues. We are particularly interested in the regulation of TOR complex 2 (TORC2), a mediator of insulin signaling in higher eukaryotes. We expect that these studies in S. pombe will lead to a better understanding of the human signaling pathways in cancers, inflammatory diseases and diabetes.

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Monday 16 March, 10:20-10:50

An evolutionarily conserved metallophosphodiesterase: bacteria, flies and the human WAGR syndrome

Sandhya S. Visweswariah

Department of Molecular Reproduction, Development and Genetics

Indian Institute of Science Bangalore 560012 INDIA

It is intriguing to come across genes that are highly conserved biochemically and structurally. In our efforts to understand the role of cAMP in mycobacteria, we identified a phosphodiesterase that was capable of cleaving cAMP. We biochemically and structurally characterized this protein, the product of the Rv0805 gene, and showed that it was a member of a large family of binuclear metallophosphoesterases. Bioinformatic analysis using the Rv0805 sequence showed that orthologs of this gene were found in bacteria, lower eukaryotes, and mammals, including humans. Interestingly, one of the human orthologs was found to be in a locus that is associated with the WAGR syndrome, a genetic disorder that leads to mental retardation, genitourinary abnormalities and Wilms tumor. The biochemical properties of the human protein, 239FB, were similar to Rv0805, but subtle differences could be discerned caused by changes in amino acid sequence at the active site. In order to study the role of orthologs of Rv0805 in a genetically tractable system, we used Drosophila melanogaster as a model, and results will be presented that show that a null of the Drosophila ortholog of Rv0805 results in diverse phenoptypes, some of which resemble those seen in WAGR patients.

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Monday 16 March, 10:50-11:20

Self-assembled lipid/DNA nanoparticles for pMDI aerosol delivery of genes to the lung

Yuhong Xu

Zhejiang-California International NanoSystems Institute

Zhejiang University, Hangzhou, China Gene therapeutics including DNAs and siRNAs are considered to have great potentials for the prevention and treatment of pulmonary diseases. But current gene delivery strategies usually require the use of viral vectors or invasive procedures with many limitations and safety concerns [4]. The delivery efficiency to the mucosal epithelial cells lining the airway surface was especially low and variable. We will reported a novel pressurized metered dose inhaler (pMDI) formulation containing self-assembled lipid/DNA nanoparticles that can deliver genes to the airway surface and achieve significant transfection efficiency. The nanoparticles are easily prepared, have reverse micellar assembly structure, and a narrow size distribution. They can be conveniently packaged and easily administered to reach the broad airway surfaces. Plasmid DNA vaccines administered in the nanoparticle pMDI formulation were shown to quickly elicit significant immune responses.

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Monday 16 March, 14:00-14:30

Application of Two-Hybrid Technology in Therapeutic Antibody Discovery

S. Benjamin Hua

Zhejiang-California International NanoSystems Institute Zhejiang University, Hangzhou, China

Human genome project generates numerous target genes for developing therapeutic monoclonal antibodies. There is also an increasing need for generating more antibodies for functional genomics applications. However, all the available antibody technologies require a purified protein as an antigen. We have developed a technology for rapidly generating fully human antibodies by simply using antigen gene. A fully human single-chain (scFv) antibody library with high complexity was constructed in a yeast two-hybrid vector. Such antibody library was used against several antigen genes for the antibody discovery. The results and development for therapeutic applications of these antibodies will be discussed in the presentation.

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Monday 16 March,14:30-15:00

Structural studies of Peptide Toxins from Indian Marine Cone Snails

Siddhartha P Sarma

Molecular Biophysics Unit, Indian Institute of Science, Bangalore – 560012

The venom of predatory marine cone snails belonging to the family Conidae have been a rich source of peptide toxins. Each species of the genus Conus is estimated to produce between 50 to 100 different peptides that are known to target various ion channels such as the sodium, potassium and calcium ion channels other pharmacologically important receptors such as the NMDA and the NACHr receptors. These peptides, which are also known as conotoxins or conopeptides are short,10 – 35 amino acid residues in length, disulfide rich peptides, in which the number of disulfides may vary from 1 to 3. Structural and pharmacological diversity among the conotoxins is achieved through variation in arrangement of cysteines in the primary sequence as well as in the disulfide pairing patterns. It is estimated that there exist over 500 species of cone snails of, which 77 species are thought to be unique to the Indian coastal waters. A program aimed at the structural and pharmacological characterization of these conopeptides has been initiated by us. The structural characterization of two novel peptides will be presented. In addition, the cloning, expression and structural characterization of a biosynthetically derived scorpion toxin will also be presented.

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Monday 16 March, 15:00-15:30

Cellular proteasome is a molecular target of organotin compounds

Guoqing Shi

Department of Biological Science and Technology, University of Science and Technology Beijing, Beijing, People’s Republic of China

The multi-catalytic proteasome controls the degradation of many cellular regulatory proteins and therefore chemicals inhibiting proteasome activity could cause the disruption of various cellular processes. It is well documented that organic tin compounds (organotins), one class of widespread persistent organic pollutants, are carcinogenic and neurotoxic, however, the involved cellular targets remain undefined. We found that the tin atom (Sn) of organotins, i.e. triphenyltin (TPT), has the highest susceptibility toward a nucleophilic attack, resembling the electrophilic ester bond carbon of the authentic proteasome inhibitor clasto-lactacystin �-lactone. Consistently, TPT binds the proteasomal chymotrypsin �5 site in an orientation and conformation suitable for a nucleophilic attack, as shown by in silico docking studies, and TPT potently and preferentially inhibits the chymotrypsin-like activity of a purified 20S proteasome (IC50 = 3.5 µmol/L) and human cellular 26S proteasome in various tumor cell lines. Direct binding of Sn to cellular proteasome is responsible for the observed irreversible inhibition, as confirmed by analyses of the chymotrypsin-like activity, �5 subunit expression, and Sn levels in the proteasome complexes. Inhibition of cellular proteasome activity by TPT results in the accumulation of ubiquitinated proteins and natural proteasome substrates, accompanied by induction of cell death. We conclude that the proteasome is a molecular target of environmental toxic organotins in human cells. The connection of organotin exposure to cellular proteasome inhibition provides a novel mechanism for environmental influences on human diseases.

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Monday 16 March, 15:50-16:10

Roles of Ca2+ and reactive oxygen species in signaling network regulating innate immunity, programmed cell death and development in plants.

Kazuyuki Kuchitsu, Takamitsu Kurusu, Haruyasu Hamada, Sachie Kimura, Hidetaka Kaya

Dept. of Applied Biological Science, Tokyo Univ. of Science, Noda, 278-8510 Japan

e-mail: kuchitsu@rs.noda.tus.ac.jp

Plants sense various molecules from pathogens to induce a series of defense responses to protect themselves against infection. Using suspension-cultured cells as model systems, we have been elucidating molecular mechanisms for signal transduction to induce expression of defense-related genes and programmed cell death (PCD). The PCD strictly depends on cell cycle (Kadota et al. Plant J. 2004), and involves reorganization of actin microfilaments and vacuoles (Higaki et al. Plant Cell Physiol. 2007). Key initial signaling events triggered by the pathogenic signals/elicitors within a minute include fluxes of ions such as Ca2+, membrane depolarization and production of reactive oxygen species (ROS) such as ･O2- and H2O2.

To reveal the molecular mechanisms and physiological significance of the stress-induced Ca2+ mobilization, we established retrotransposon-insertional knockout lines as well as the overexpressing lines of a putative voltage-gated Ca2+ permeable channel, OsTPC1, in rice. The OsTPC1 overexpressor showed enhanced sensitivity to a proteinaceous elicitor, whereas the elicitor-induced defense responses including activation of a MAP kinase and PCD were strongly suppressed in the knockout cells, which was rescued by expression of OsTPC1 (Kurusu et al. Plant J. 2005). The gene expression profiles as well as changes in cytosolic Ca2+ concentration induced by various stresses are being comparatively analyzed between the knockout and the wild type lines. Plant respiratory burst oxidase homolog (rboh) proteins have been implicated in ROS production not only in stress responses but also during development. Unlike most of the mammalian counterparts, they have extended hydrophilic N-terminal regions containing two EF-hand motifs. By employing a heterologous expression system, we showed that ROS production by Arabidopsis thaliana rbohD and rbohC/RHD2 were induced by ionomycin, a Ca2+ ionophore. This activation required a conformational change in the EF-hand region, as a result of Ca2+ binding to the EF-hand motifs. AtrbohD was directly phosphorylated in vivo, and that this was enhanced by a protein phosphatase inhibitor, calyculin A (CA). CA itself induced ROS production and dramatically enhanced the ionomycin-induced ROS production. These results suggest that Ca2+ binding and phosphorylation synergistically activate the rboh-mediated ROS-production that governs stress responses and development including root hair growth (Ogasawara et al. J. Biol. Chem. 2008; Takeda et al. Science 2008). Possible signal propagation due to positive feedback regulation of Ca2+ mobilization and ROS production will also be discussed.

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Monday 16 March, 16:10-16:40

The NAC domain transcription factor Suppressor of Gamma Response 1 (Sog1) governs programmed response to DNA damage

A. B. Britt*a, K. Yoshiyamaa, T. Furukawaa, P. Conklina, M. Curtisb, and John Haysb

*a Department of Plant Biology,

University of California, Davis, CA 95616 *b Department of Environmental and Molecular Toxicology,

Oregon State University, Corvallis, OR 97331 All living things possess mechanisms to detect the presence of DNA damage and transduce that signal to induce a variety of responses. These responses include the activation of repair, the arrest of the cell cycle, and the induction of programmed cell death. In Arabidopsis the response to chromosome-breaking agents includes the robust upregulation of hundreds of genes, including many genes that are clearly involved in DNA repair. This is a specific response to double strand breaks: the spectrum of genes induced by gamma radiation does not include the genes known to be induced by a variety of other abiotic stressors, and the transcriptional response is entirely dependent on the PI3K-like protein kinase ATM, a protein known to be activated by double strand breaks. Such a response is unprecedented- mammals and yeast do not exhibit this robust and specific induction of repair-related genes in response to double strand breaks. As a result of a search for mutants defective in gamma-induced cell cycle arrest, a line carrying a "gamma resistant" mutation, termed sog1, was identified. This mutation was mapped and cloned, and SOG1 was revealed to be a member of the large family of NAC domain transcription factors. Further analysis of sog1 revealed that this gene, like ATM, is required for the transcriptional response to gamma radiation. Here we will present evidence that SOG1 is also required for the programmed, tissue-specific cell death response to DNA damage observed in Arabidopsis. Thus SOG1, although unrelated to the mammalian transcription factor and tumor suppressor TP53, evolved independently in multicellular plants to play the same essential role in governing DNA damage response.

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Monday 16 March, 16:40-17:10

The Promoter Code: Insights into eukaryote transcription from plant transcription factors and their DNA-motif companions

Dierk Wanke,

Center for Molecular Plant Biology,

Tübingen University, Tübingen, Germany

DNA sequences harbor the essential information to control specific gene expression changes and integrate information from upstream laying signaling cascades. This is mediated by direct binding of proteins, e.g. transcription factors, to defined stretches of DNA in regulatory regions. The analysis of these DNA regions is still a challenging task: Here, several signaling pathways merge to result in an orchestrate gene expression response. In contrast, surprisingly little is known on how this integration at the transcriptional level takes place. We use the invaluable combination of functional approaches in the laboratory and computer aided sequence analysis for regulatory sequence analysis. An initial examination of eukaryote promoter sequences revealed that about 80% of all promoters lack a TATA-box signature. On the other hand, 20 % of all known eukaryote cis-regulatory elements are enriched in front of a gene. In a cross species comparison, we could identify several putative functional cis-regulatory elements conserved in most eukaryote promoters. We use Arabidopsis thaliana as a genetic model for functional analyses, as plant promoters are amongst the best understood eukaryote promoters. In the last few years, we and others performed large, directly comparable microarray with the plant model organism Arabidopsis thaliana experiments in the AtGenExpress project. With the combined use of our knowledge on cis-regulatory elements and transcript profiling we infer signaling cascades and regulatory networks to understand how specific stress responses are generated. To test the biological relevance of our findings, we established several techniques for Arabidopsis thaliana to study transcription factor function in vitro and in vivo.

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Monday 16 March, 17:10-17:40

Evolutionary conserved essential proteins in the chloroplast outer membrane - from endosymbiosis to membrane biogenesis

Kentaro Inoue

Department of Plant Sciences

University of California, Davis, CA 95616 Chloroplasts of higher plants and algae house numerous metabolic reactions including photosynthesis to support the life of almost all organisms on earth. Chloroplasts have evolved from an ancestral cyanobacterium by endosymbiosis, which requires gene transfer and depends on establishment of protein import apparatus at the double-membrane envelope. Toc75 is one of the core components of the import apparatus at the outer envelope, serving as a protein-conducting channel. We have been using Toc75 as a tool to address various questions relevant to the mechanism of chloroplast biogenesis. By in vitro assays, we identified a unique polyglycine stretch near the N-terminus of Toc75 as a signal necessary for proper sorting to the chloroplast envelope. Biochemical and genetic studies allowed us to discover that plastidic type I signal peptidase 1 (Plsp1) is involved in complete maturation of Toc75. Interestingly, Plsp1 plays a vital role for thylakoid development, which is independent of Toc75 maturation. Finally, we identified OEP80, a Toc75 paralog that appears to have diverged early in the evolution of chloroplasts from their common ancestor with modern cyanobacteria, and showed that it is essential for chloroplast biogenesis but may have a function different from that of Toc75. Supported by USDA-CSREES and US-DOE Energy Biosciences Program.

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Monday 16 March, 17:40-18:10

The Application of Biotechnology and Genomics to Plant Breeding

Allen Van Deynze,

Seed Biotechnology Center, University of California, Davis, USA, 95616

Plant biotechnology encompasses molecular biology, tissue culture and transgenics. Each is a tool that can accelerate and sometimes make plant breeding more precise. The UC Davis Seed Biotechnology Center (SBC) focuses on applied research bringing lab discoveries closer to application. Specifically, the SBC has developed novel methods to rapidly incorporate molecular markers into breeding of vegetable and agronomic crops using microarray and ultra�high throughput technologies. Genetic maps, expression and metabolomics are being used to identify markers and clone genes such as high temperature germination in lettuce. Transgenic technologies are being used to increase the tolerance of crops to water stress. To use biotechnology, the biology of crops and environmental impacts of novel traits must be defined to meet government regulations. The SBC is providing research such as gene flow studies in crops to enable commercialization of novel traits. An integrated approach is essential to ensure that the best technologies can be leveraged for crop improvement.

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Titles of Posters at Poster Session

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(Note: Order will be changed.) Aoki Group, Faculty of Pharmaceutical Sciences １ Photochemical Cleavage Reaction of 8-Quinolinyl Sulfonates in Aqueous Solution:

Mechanism and Application to Biomedical Methodologies. Kengo Hanaya(1) Yoshiyuki Kageyama(1) Aya Kamikawa(1) Megumi Tsunoda(1) Masanori Kitamura(1,2) and Shin Aoki(1,2) (1) Faculty of Pharmaceutical Sciences, Tokyo University of Science (2) Center for Drug Delivery Research, Tokyo University of Science

2 Repair of DNA Photolesions Utilizing Photoreactive Zinc(II) Complexes of Macrocyclic

Polyamines in Aqueous Solution Mari Itoh (1) Masanori Kitamura(1,2) Yoshiyuki Kageyama,(1) and Shin Aoki(1,2) (1) Faculty of Pharmaceutical Sciences, Tokyo University of Science (2) Center for Drug Delivery Research, Tokyo University of Science

3 Molecular Recognition in Aqueous Solution Utilizing Supramolecular Complexes

Formed by Self-Assembly of Multinuclear Zinc(II) Complexes and Polyanionic Compounds. Mohd Zulkefeli(1) Satoshi Suzuki(1) Hanae Ueyama(1) Masanori Kitamura(1,2) and Shin Aoki(1,2) (1) Faculty of Pharmaceutical Sciences, Tokyo University of Science (2) Center for Drug Delivery Research, Tokyo University of Science

Inoue Group, Department of Applied Biological Science 1． Role of manganese in low-pH-induced root hair formation in Lactuca sativa L. cv. Grand

Rapids seedlings Konno M., Ooishi M. & Inoue Y. Dept. of Applied Biological Science, Tokyo University of Science

2. Chlorogenic acid facilitates root hair formation in lettuce seedlings

Narukawa M., Kanbara K., Tominaga Y., Aitani Y., Fukuda K., Kodama T., Murayama N., Nara Y., Arai T., Konno M., Kamisuki S., Sugawara F., Iwai M. & Inoue Y. Dept. of Applied Biological Science, Tokyo University of Science

3. Plugging a Molecular Wire into Photosystem I: Reconstitution of the Photoelectric

Conversion System on a Gold Electrode Iwai M., Inoue Y., Terasaki N., Yamamoto N., Hiraga T., Yamanoi Y., Yonezawa T., Nishihara H., Ohmori T., Sakai M., Fujii M., Tohri A., Yoneyama S., Minakata M., & Enami I. Dept. of Applied Biological Science, Tokyo University of Science

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Kamakura Group, Department of Applied Biological Science 1 Involvement of Magnaporthe oryzae Chitin-Binding Protein Gene, CBL1, in

Appressorium Differentiation. Sayaka MURATA, Yuichi NAKAJIMA, Yuko OHNO, and Takashi KAMAKURA. Dept. of Applied Biological Science, Tokyo University of Science

2 Search of the gene related to D-arabinose metabolism in novel species of Lactobacilli,

Lactobacillus nodensis. Tomoko KASHIWAGI, Natsuko NAGURA, Tomonori SUZUKI, Takashi KAMAKURA. Dept. of Applied Biological Science, Tokyo University of Science

3 Characterization of the histone deacetylase MoHDA1 in Magnaporthe oryzae

Masumi IZAWA1, 2, Makoto KIMURA2, Minoru YOSHIDA2, Takashi KAMAKURA1 1 Faculty of Science and Technology, Tokyo Univ. of Science, Noda, Japan. 2 ASI, RIKEN, Wako, Japan. Dept. of Applied Biological Science, Tokyo University of Science

4 Search for neoechinulinA biosynthesis genes by phage display method.

Momoko HORIUCHI, Takeroh YAGI, Naoki TOMINAGA, Takashi KAMAKURA. Dept. of Applied Biological Science, Tokyo University of Science

Kuchitsu Group, Department of Applied Biological Science 1 Regulation of pathogenic elicitor-induced defense responses and programmed cell death

by Ca2+ signaling network: functional analyses of a putative voltage-gated Ca2+ channel and Ca2+-activated protein kinases.

*Takamitsu Kurusu, Haruyasu Hamada, Jumpei Hamada, Hiroshi Nokajima, Youichiro Kitagawa, Kazuyuki Kuchitsu, Dept. of Applied Biological Science, Tokyo University of Science

2 Interrelationship between innate immunity and cell cycle regulation in Arabidopsis:

flg22-induced defense responses and cell-cycle arrest in synchronous-cultured MM2d cells.

*Shinya Takahashi1, Ryoko Ohno1, Yutaka Maeda1, Sachie Kimura1, Yuki Abe1, Hidetaka Kaya1, Masaaki Umeda2, Kazuyuki Kuchitsu1

1 Dept. of Applied Biological Science, Tokyo University of Science 2 Dept. of Biological Science, Nara Institute of Science and Technology 3 Production of reactive oxygen species in plant signaling network: Regulation of

ROS-producing enzymes, AtrbohD and AtrbohC, by Ca2+. *Hidetaka Kaya, Sachie Kimura, Haruka Hishinuma, Eriko Senzaki, Kazuyuki

Kuchitsu Dept. of Applied Biological Science, Tokyo University of Science

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4 Molecular mechanism for activation of Arabidopsis NADPH oxidase AtrbohF by Ca2+

and phosphorylation. *Sachie Kimura, Haruka Hishinuma, Eriko Senzaki, Tomoko Kawarazaki, Masataka

Michikawa, Hidetaka Kaya, Kazuyuki Kuchitsu Dept. of Applied Biological Science, Tokyo University of Science Sakaguachi Group, Department of Applied Biological Science 1 Analysisi of DNA in Liquid Crystal Kazuki Iwabata. Dept. of Applied Biological Science, Tokyo University of Science 2 Development of novel biotechnology using inorganic materials Keita Ino. Dept. of Applied Biological Science, Tokyo University of Science 3 Analysis of the eukaryotic DNA polymerase Hirohumi Kodera. Dept. of Applied Biological Science, Tokyo University of Science Taguchi Group, Department of Applied Biological Science 1 Crystallographic and mutational analysis of the allosteric L-lactate dehydrogenase from

Lactobacillus casei Kazuhito Arai. Dept. of Applied Biological Science, Tokyo University of Science

2 Structure-function relationship in D-2-hydroxyacid dehydrogenase Superfamily

Kazuhito Arai. Dept. of Applied Biological Science, Tokyo University of Science Sugawara Group, Department of Applied Biological Science 1. Isolation of Natural Products (1). Takuma Kimura. Dept. of Applied Biological Science, Tokyo University of Science 2. Isolation of Natural Products (2). Yoshihiro Sato. Dept. of Applied Biological Science, Tokyo University of Science 3. Synthesis of Natural Products (1) the Radio Sensitizer SQ Series. Hiroshi Murata. Dept. of Applied Biological Science, Tokyo University of Science 4. Synthesis of Natural Products (2) Bioactive Compounds. Hiroaki Ishii, Kyohei Shimizu, Satomi Shimura. Dept. of Applied Biological Science,

Tokyo University of Science 5. Development of Phage Display with Quarts Crystal Microbalance Method. Tomoe Kusayanagi. Dept. of Applied Biological Science, Tokyo University of Science

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6. A facile Method to Inhibit Protein-Protein Interactions with Phage Display Method. Takeki Saitoh. Dept. of Applied Biological Science, Tokyo University of Science 7. Antitumor Antibiotic Fostriecin Targets Cystein-269 of the Protein Phosphatase 2A

Catalytic Subunit in Mammalian Cells with A Covalent Bond. Toshifumi Takeuchi. Dept. of Applied Biological Science, Tokyo University of Science Koiwai Group, Department of Applied Biological Science 1. BPOZ-2 directly binds to eEF1A1 to promote eEF1A1 ubiquitylation and degradation

and prevent translation. Kotaro Koiwai, So Maezawa, Kousuke Kouda, Takahide Hayano and Osamu Koiwai. Dept. of Applied Biological Science, Tokyo

University of Science 2. E3-independent and BPOZ-2/CUL3-dependent ubiquitylation of TdT. So Maezawa, Kotaro Koiwai, Kousuke Kouda, Takahide Hayano and Osamu Koiwai.

Dept. of Applied Biological Science, Tokyo University of Science Arai Group, Department of Applied Biological Science 1. Redox regulation of microtubule polymerization by glutathionylation.

〇Takuro Koshiyama, Fuyuki Kametani, Masato Hasegawa, Nobuo Watanabe, Takao Arai, Dept. of Applied Biological Science, Tokyo University of Science

2. Anti-Thy-1 antibodies can suppress PC12 cell death induced by cytocidal agents that

cause ROS production. 〇Mitsuhiro Nakashima, Nobuo Watanabe, Takao Arai, Dept. of Applied Biological Science, Tokyo University of Science

3. The role of glutaredoxin-1 in defense against nitrosative stress.

〇Yoshihiko Saito, Nobuo Watanabe, Takao Arai, Dept. of Applied Biological Science, Tokyo University of Science

4. SIN-1 cytotoxicity to PC12 cells is mediated by thiol-sensitive short-lived substances

generated through SIN-1 decomposition in culture medium 〇Kanako Konishi, Nobuo Watanabe, Takao Arai, Dept. of Applied Biological Science,

Tokyo University of Science

Kagurazaka Campus

Bldg. No. 1

Site for redevelopment

Wakamiya Bldg.

Morito Memorial Hall

Bldg. No. 5(Research Institute for Chemistry and Related Disciplines and Kagurazaka Gymnasium)

Bldg. No. 6

MIP

Research Center for Nanoscience and Nanotechnology

Science and Technology Museum

Bldg. No. 10

Bldg. No. 11

Fujimi Bldg.

Futaba Bldg.

Kudan Campus

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Centennial Library

Bldg. No. 9

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Frontier Research Center for Computational Sciences

Large Lecture Hall Bldg.

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Faculty of Pharmaceutical Sciences Bldg. No. 14

Faculty of Pharmaceutical Sciences Bldg. No. 15

Genome and Drug Research Center

Research Center for DDS

Information Media Center

Research Institute for Biological Sciences

21st Century COE Fire Science Research Center

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University of California, Davis

University of California, Los Angeles

University of California, San Diego

University of California, Santa Barbara

University of California, Santa Cruz

Ohio State University

University of Tuebingen

Zhejiang University

University of Science and Technology, Beijing

Indian Institute of Science

Nanyang Technological University

Collaboration and Invited Universities

15(Sun) and 16(Mon) March 2009Hotel Metropolitan Edmont, Banri(2F)

17(Tue) March 2009 Round Table Discussion and Campus Tour at Noda

Biological Science and Technology

3rd Tokyo University of ScienceInternational Collaboration Workshop

(TUS-ICW)Joint Hosting:Division of Chemical Biology etc, Research Institute for Science and Technology

Workshop Program

HotelMetropolitan Edmont

InternationalExchange Office

Iidab

ashi

Sta. JR

Tokyo Universityof Science

Topics

Tokyo University of ScienceCenter for Promotion of Internationalization

Workshop Secretariat

International Exchange Office1-3 Kagurazaka, Shinjuku-ku, Tokyo, 162-8601 JAPANPhone : +81-(0)3-5228-8726 FAX : +81-(0)3-5228-8727HP : http://www.tus.ac.jp/enE-mail : intlexchg@admin.tus.ac.jp

Workshop Place

Hotel Metropolitan Edmont, Banri(2F)3-10-8 Iidabashi, Chiyoda-ku, Tokyo, 102-8130 JAPANPhone: +81-(0)3-3237-1111