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ICSB-2006

The 7th International Conference on Systems BiologyOctober 8 - 13, 2006

Pacifico Yokohama, Yokohama, Japan

CONTENTSWelcome to ICSB-2006 ..............................................................................2

Committees ..............................................................................................3

Program Day 1 (October 9) .................................................................4

Day 2 (October 10) ................................................................5

Day 3 (October 11) ................................................................6

Program At-A-Glance .................................................................................9

Student Session (October 10) ..................................................................10

Session Abstracts

Plenary Talk Abstracts .........................................................................11

I Systems Biology for Medicine .......................................................13

II Systems Biology of Basic Biological Systems ...............................19

III Fronts in Systems Biology .............................................................27

Poster Session .........................................................................................34

Tutorial Program (October 8) ...................................................................48

Workshops (October 7,12,13) .................................................................49

Access ............................................................................................50

Floor Plan ............................................................................................51

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Welcome to ICSB-2006

Welcome to the Seventh International Conference on Systems Biology!

The International Conference on Systems Biology (ICSB) started in 2000 in Tokyo, and traveled around the world—Pasadena, Stockholm, St. Louis, Heidelberg, and Boston. Owing to the efforts of organizers, sponsors, and participants, the conference has grown into the main conference in the field. This year, ICSB employed parallel sessions for the first time, and invited over 65 distinguished speakers in the field reflecting the overall landscape of systems biology today. With about 400 posters, 12 tutorial sessions, and 5 workshop programs, ICSB-2006 presents the most comprehensive program to date. The program was enabled by generous support from several government agencies and sponsor companies for which we, as the systems biology community, are very grateful.

When the f irst ICSB was held in 2000 at Tokyo with the support of Japan Science and Technology Corporation (JST), systems biology was yet to be recognized as a serious area of study. Nevertheless, it attracted over 300 attendees, over a half of them from outside of Japan. That year featured Prof. Sydney Brenner, a Nobel Laureate in physiology or medicine in 2002, as a banquet speaker. Systems biology is now gaining serious attention world-wide and a number of major research programs and centers have been created. It is my great pleasure that ICSB has grown into the main forum of scientific discussions in systems biology, and has contributed to the field’s progress. However, we should remind ourselves that the field is still in its infancy and much more needs to be done in all areas of research to bring still more maturity to the field. Given the long history of pioneering research leading to the modern form of systems biology, the field may have finally arrived to the point of experiencing a steep learning curve. A scientific problem, experimental techniques, computational analysis, and theoretical frameworks all have to be aligned to address significant questions in biology and decipher their system-level properties and principles. You will witness the growth and future of systems biology at ICSB-2006.

Please enjoy the conference and beautiful Japan!

Sincerely yours,

Hiroaki KitanoConference Chair, The Seventh International Conference on Systems Biology

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Committees*alphabetical order by region

Program CommitteeAsia:Uri Alon (Weitzman Institute of Science, Israel)Upi Bhalla (National Centre for Biological Science, India)Kwang-Hyun Cho (Seoul National Univ., Korea)Hsuan-Cheng Huang (National Yang-Ming University,

Taiwan)Akira Funahashi (SBI & JST ERATO-SORST Kitano

Project, Japan)Mariko Hatakeyama (RIKEN GSC, Japan)Yoshihide Hayashizaki (RIKEN GSC, Japan)Do Han Kim (Gwangju Institute of Science and Technology,

Korea)Hiroaki Kitano (SBI & Sony CSL, Japan) Conference

ChairShinya Kuroda (Univ. of Tokyo, Japan)Sang Yup Lee (Korea Advanced Institute of Science and

Technology, Korea)Edison Liu (Genome Institute of Singapore, Singapore)Douglas Murray (SBI & JST ERATO-SORST Kitano

Project, Japan)Shuichi Onami (Keio Univ., Japan)Reiko Tanaka (RIKEN BioMimetic Center, Japan)Masaru Tomita (Keio Univ., Japan)Hiroki Ueda (RIKEN CDB, Japan)

Europe:Lilla Alberghina (Univ. of Milano-Bicocca, Italy)Marta Cascante (Univ. of Barcelona, Spain)Roland Eils (DFKI (=German Cancer Research Center),

Germany)Peter Ghazal (GTI (=Scottish Centre for Genomic

Technology and Informatics), UK)Igor Goryanin (Univ. of Edinburgh, UK)Stefan Hohmann (Goteborg Univ., Sweden)Douglas Kell (Univ. of Manchester, UK)Edda Klipp (Max-Planck Institute for Molecular Genetics,

Germany)Pierre De Meyts (Hagedorn Research Institute, Denmark

and Novo Nordisk A/S)Jens Nielsen (DTU (=Technical Univ. of Denmark), Denmark)Staffan Normark (Karolinska Institute, Sweden)Nicolas Le Novere (EBI (=European Bioinformatics

Institute), UK)Klaus Prank (GlaxoSmithKline)Hans Westerhoff (Univ. of Amsterdam, the Netherlands)

North America:Adam Arkin (Lawrence Berkeley National Lab., USA)Frederick Cross (Rockefeller Univ., USA)Marie Csete (Emory Univ. USA)Francis Doyle (UCSB, USA)John Doyle (Caltech, USA)Joe Gray (Lawrence Berkeley National Lab. USA)Mike Hucka (Caltech, USA)Trey Ideker (UCSD, USA)Boris Kholodenko (Thomas Jefferson Univ., USA )Douglas Lauffenburger (MIT, USA)Pedro Mendes (Virginia Tech., USA)Bernhard Palsson (UCSD, USA)John Tyson (Virginia Tech., USA)Marc Vidal (Dana-Farber Cancer Institute, USA)Tau-Mu Yi (UCI, USA)

Student Session Organizer:Satya Arjunan (Keio Univ., Japan)John Cumbers (Brown Univ., USA)

Advisory CommitteeSydney Brenner (Founding President, Okinawa Institute of

Science and Technology & The Salk Institute)Kiyoshi Kurokawa (President, The Science Council of

Japan)Koichi Kitazawa (Senior Executive-Director, Japan

Science and Technology Agency)Yoshiyuki Sakaki (Director, RIKEN GSC)Sin-ichi Nishikawa (Deputy Director, Laboratory for

Stem Cell Biology, Center for Developmental Biology, RIKEN)

Yoshiki Hotta (President, Research Organization of Information and Systems)

Shigetada Nakanishi (Director, Osaka Bioscience Institute)

Executive CommitteeKazuyuki Aihara (Univ. of Tokyo and JST ERATO Aihara

Project)Akiyasu Fujii (SBI)Ken Fukuda (AIST)Akira Funahashi (SBI & JST ERATO-SORST Kitano

Project)Mariko Hatakeyama (RIKEN GSC)Hiroaki Kitano (SBI & Sony CSL)Tatsuhiko Kodama (Univ. of Tokyo)Shinya Kuroda (Univ. of Tokyo)Yukiko Matsuoka (SBI & JST ERATO-SORST Kitano

Project)Satoru Miyano (Univ. of Tokyo)Masahiko Noda (Japan Science and Technology Agency)Makoto Suematsu (Keio Univ. School of Medicine)Hiroki Ueda (RIKEN CDB)Toru Yao (RIKEN GSC)

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Program

Day 1: Monday, October 9, 2006

9:30 Opening 1F Main HallSpeaker

Hiroaki Kitano, The Systems Biology Institute, Sony Computer Science Laboratories, Inc.

10:00 P1 Plenary Session 1 1F Main HallElectricity meets Chemistry: Fast and Slow Signaling in Memory

Upinder S. Bhalla, National Centre of Biological Sciences

10:30 P2 Plenary Session 2 1F Main HallSpatio-temporal Patterns of Intracellular Signaling

Atsushi Miyawaki, RIKEN Brain Science Institute

11:00 Break

11:30 P3 Plenary Session 3 1F Main HallBiological Large Scale Integration

Stephen R. Quake, Stanford University / HHMI

12:00 P4 Plenary Session 4 1F Main HallEvolvability and hierarchy in rewired bacterial gene networks

Luis Serrano, European Molecular Biology Laboratory

12:30 Lunch Session Talks

14:00 S1a Systems Biology for Drug Discovery 1F Main Hall

Chairs John Morser, Nihon Schering Research Center Osamu Sato, Dai-ichi Pharmaceuticals

SpeakersFrom Molecular Events to Clinical Outcome: Computational Systems Biology in the Pharmaceutical Industry

Klaus Prank, GlaxoSmithKlineHarnessing Systems Biology Using Chemical Synergies

Joseph Lehár, CombinatoRX, Inc.Application of Systems Biology for Pharmaceutical Drug Development

Jeff Trimmer, Entelos Inc.Systems Biology in Drug Discovery and Development: Impact and Challenges

Didier Scherrer, AstraZenecaTechnological breakthrough for cell-based target discovery

Masato Miyake, CytoPathfinder Inc.

14:00 S1b Cyclic and Dynamic Behaviours 5F Sub Hall 1

Chairs Hiroki Ueda, RIKEN Center for Developmental Biology Lilia Alberghina, University of Milano-Bicocca

SpeakersA Generic Model of Cell Cycle Regulation in Eukaryotes

John J. Tyson, Virginia TechProbing structure and dynamics of cell cycle in budding yeast

Lilia Alberghina, University of Milano-BicoccaCircadian Systems of Cyanobacheria

Takao Kondo, Nagoya UniversityAnalysis and Synthesis of Mammalian Circadian Clocks

Hiroki Ueda, RIKEN Center for Developmental BiologyMulti-loop Architecture in Clock Circuits

Andrew J. Millar, University of Edinburgh

16:30 -18:00

Poster Session I 4F

18:00 Welcome Reception 5F

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Day 2: Tuesday, October 10, 2006

9:30 P5 Plenary Session 5 1F Main HallDealing with the complexity of a 'simple' eukaryotic cellStephen G. Oliver, The University of Manchester

10:00 Break Session Talks

10:30 S2a Cardiovascular Systems Biology 1F Main Hall

Chair Do Han Kim, Gwangju Institute of Science and Technology

Speakers Cardiac Systems Biology

Giovanni Paternostro, Burnham Institute for Medical Research, La Jolla, CAKyoto Model, a comprehensive cardiac cell model

Akinori Noma, Kyoto University, Graduate School of MedicineCardiomyopathy in Mice and Men

Jonathan Seidman, Harvard Medical SchoolDirect observation of transcription in the human cell using tiling array

Tatsuhiko Kodama, The University of Tokyo

10:30 S2b Yeast Systems Biology 5F Sub Hall 1

Chairs Stefan Hohmann, Goteborg University Stephen G. Oliver, The University of Manchester

Speakers Dynamic Modeling of Stress Response of Yeast Cells

Edda Klipp, Max Planck Institute for Molecular GeneticsQuantitative physiology of a cellular information sensing and relaying system

Roger Brent, The Molecular Sciences InstituteInterrogation of cellular networks

Mike Tyers, Samuel Lunenfeld Research InstituteSources and control of cell to cell variation in the response of yeast to mating pheromone

Alejandro Colman-Lerner, The Molecular Sciences Institute

10:30 S2e Network Biology 5F Sub Hall 2

Chairs Marc Vidal, Dana-Farber Cancer Institute / Harvard Medical School Yoshihide Hayashizaki, RIKEN Yokohama Institute

Speakers Interactome Networks

Marc Vidal, Dana-Farber Cancer Institute / Harvard Medical SchoolProtein Network Comparative Genomics

Trey Ideker, University of California, San DiegoGenome Network Project in Japan

Yoshihide Hayashizaki, RIKEN Yokohama InstituteSingle molecule imaging of motor proteins in living cells - deciphering physical networks of molecular motions

Hideo Higuchi, Tohoku University

12:30 Lunch Session Talks

14:00 S2d Systems Immunology 1F Main Hall

Chair Marie Csete, Emory University

Speakers Evolution and divergence of herpesviral protein interaction networks

Juergen Haas, University of MunichPathway Biology Approach to the Interferon System

Peter Ghazal, University of Edinburgh Medical SchoolThe Center for Inflammation and Regenerative Medicine: a service model

Gilles Clermont, University of PittsburghTo Kill or not to Kill - Decision making in Natural Killer Cells

Roland Eils, German Cancer Research Center (DKFZ), HeidelbergStem Cells and Pain: Linking Immunity to Regeneration

Marie Csete, Emory University

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14:00 S2c Metabolomics and Bioprocess 5F Sub Hall 1

Chairs Sang Yup Lee, KAIST Marta Cascante, University of Barcelona

Speakers Bottom-up Reconstruction of the Human Metabolic Network based on Build-35 and Bibliomic Data

Bernhard Palsson, University of California, San DiegoSystems Level Analysis and Engineering of Industrial Bacteria

Sang Yup Lee, KAISTMetabolome Analysis and Synthetic Biology

Masaru Tomita, Keio UniversityA Systems Biology Approach to Identify and Therapeutically Exploit the Weakness of the Robust Tumour Metabolism

Marta Cascante, University of Barcelona

14:00 S2f Student Session 5F Sub Hall 2

Chair Marc Vidal, Dana-Farber Cancer Institute / Harvard Medical School

Speakers Silvia Jantos, EMBLMikael Andersen, Technical University of DenmarkYusuke Maeda, The University of TokyoDale Muzzey, MIT- Harvard Alexander Fletcher, University of OxfordAriosto Silva, Centro Infantil Boldrini

16:30-18:30

Poster Session II 4F

19:00 Banquet Pan Pacific Hotel

Day 3: Wednesday, October 11, 2006Session Talks

9:15 S3a Systems Biology of Diabetes (Novo Nordisk-sponsored) 1F Main Hall

Chair Pierre De Meyts, Hagedorn Research Institute

Speakers Understanding diabetes pathogenesis: the need for systems biology

Pierre De Meyts, Hagedorn Research InstituteA Systems Biology Approach to Type 1 Diabetes

Allan E. Karlsen, Novo Nordisk A/SThe transcriptome as a window into pathogenesis of type 1 diabetes

Nathan Goodman, Institute for Systems Biology

9:15 S3b Developmental Systems Biology 5F Sub Hall 1

Chairs Shuichi Onami, RIKEN Genomic Sciences Center Fabio Piano, New York University

SpeakersC. elegans early embryogenesis: global, local and evolutionary views

Fabio Piano, New York UniversityInteractions among the Pigment Cells of Zebrafish Give Rise to Turing Pattern

Shigeru Kondo, Nagoya UniversityQuantitative analysis of C. elegans embryogenesis

Shuichi Onami, RIKEN Genomic Sciences Center

9:15 S3c Complex Systems Biology 5F Sub Hall 2

Chairs Kwang-Hyun Cho, Seoul National University Sree N. Sreenath, Case Western Reserve University

Speakers Interaction Balance Coordination as Organizing Principle in Complex Systems Biology

Mihajlo D. Mesarovic, Case Western Reserve UniversityCoordination of Gene Expression by RNA Operons

Jack Donald Keene, Duke University Medical CenterApplications of Complex Systems Biology to the Study of Neural Systems

Kenneth Alan Loparo, Case Western Reserve University

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10:30 Break Session Talks

11:00 S3d Cancer Systems Biology 1F Main Hall

Chairs Roland Eils, German Cancer Research Center (DKFZ), Heidelberg Charles Auffray, CNRS and Pierre & Marie Curie University

Speakers Design Principles of the JAK-STAT Signaling Pathway

Ursula Klingmüller, German Cancer Research Center (DKFZ), HeidelbergPredicting the Outcome of Chemotherapy through Pathway Modelling

Charles Auffray, CNRS and Pierre & Marie Curie UniversityFrom Simulation to Therapy: A Systems Biology Approach to Oncogene Detection

Avijit Ghosh, Drexel University

11:00 S3e Systems Neurobiology 5F Sub Hall 1

Chairs Upinder S. Bhalla, National Centre of Biological Sciences Boris N. Kholodenko, Thomas Jefferson University Nicolas Le Novere, EMBL-EBI

Speakers Understanding Molecular Complexity at the Neuronal Synapse

August B. Smit, Vrije Universiteit AmsterdamModelling Structure and Function of the Post-Synaptic Proteome

James Douglas Armstrong, University of EdinburghSystems Analysis of Spike-Timing Dependent Synaptic Plasticity

Shinya Kuroda, The University of Tokyo

11:00 S3f Control and System Theory for Systems Biology 5F Sub Hall 2

Chairs Francis J. Doyle, University of California, Santa Barbara Rudi Gunawan, National University of Singapore

Speakers Robustness Analysis of Biological Networks Using Sensitivity Measures

Francis J. Doyle, University of California, Santa BarbaraFeedback Control Regulation of Cell Division

Pablo A. Iglesias, The Johns Hopkins UniversityThe Architecture of Cellular Regulation

John Doyle, California Institute of Technology

12:30 Lunch Session Talks

14:00 S3g Synthetic Biology 1F Main Hall

Chair Drew Endy, Massachusetts Institute of Technology

Speakers Languages and Grammars for Programming in DNA

Drew Endy, Massachusetts Institute of TechnologyApplications in Systems and Synthetic Biology

Adam Arkin, University of California, BerkeleyImpact of a Whole Genome Cloning on Systems Biology

Mitsuhiro Itaya, Keio UniversityAdaptive Response of a Gene Network to Environmental Changes by Fittness-induced Attractor Selection

Tetsuya Yomo, Graduate School of Information Science and Technology, Osaka UniversityProgrammable Bacterial Catalysts

Vitor Martins dos Santos, Helmholtz Centre for Infection Research

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14:00 S3h Signal Transduction 5F Sub Hall 1

Chairs Philippe Bastiaens, EMBL Heidelberg Boris N. Kholodenko, Thomas Jefferson University Shinya Kuroda, The University of Tokyo

Speakers Cell-signaling Dynamics in Time and Space

Boris N. Kholodenko, Thomas Jefferson UniversityEmerging Principles of Living Systems

Hans V. Westerhoff, Manchester Centre for Integrative Systems Biology and Biocentre AmsterdamLigand-dependent Cell Fate Control of ErbB Signaling Network in Breast Cancer Cells

Mariko Hatakeyama, RIKEN Genomic Sciences CenterRules for Modeling Signal-transduction Systems

William S. Hlavacek, Los Alamos National LaboratoryReaction Cycles in the Spatial and Temporal Organization of Cell Signaling

Philippe Bastiaens, EMBL Heidelberg

14:00 S3i Novel Computational Environments for Systems Biology 5F Sub Hall 2Chairs Douglas Kell, The University of Manchester

Pedro Mendes, Virginia Tech.

Speakers Linking Text with Knowledge - Challenges in Text Mining for Biology

Junichi Tsujii, The University of TokyoGoing with the Flow: Distributed Computing for Systems Biology using Taverna

Carole Anne Goble, The University of ManchesterThe DREAM project: Establishing a Community-based Gold Standard for Systems Biology

Andrea Califano, Columbia University Medical CenterThe Systems Biology Markup Language (SBML): Where It's Been and Where It's Going

Michael Hucka, California Institute of TechnologyMIRIAM and BioModels DB: Curation and Exchange of Quantitative Models

Nicolas Le Novere, EMBL-EBI

16:30 Break

17:00 Panel Discussion 1F Main Hall

Perspective on Systems Biology in National Research Agenda

Chairs Hiroaki Kitano Stefan Hohmann

17:30 Closing 1F Main Hall

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SundayOctober 8

Pacifico Yokohama411 + 412 413 414 + 415 416 417 418 419

9:30 T2:SignalingNetwork(CellNetAnalyzer)

T1:Design Principle

T3:New Math Method

T12:SBML

T8:Copasi Basic

T11:PottersWheel

T7:Virtual Cell

12:3014:00

T4:MatLab

T5:Teranode

T 6:E-Cell

T9:Copasi Advanced

T10:CellDesigner

17:00

MondayOctober 9

Pacifico Yokohama1F Main Hall 4F 5F Sub Hall 1 5F

9:00

Poster Display

9:30 Opening10:00 P1

Upinder S. Bhalla10:30 P2

Atsushi Miyawaki11:00 Break11:30 P3

Stephen Quake12:00 P4

Luis Serrano12:30 Lunch14:00 S1a

Drug DiscoveryS1b

Cyclic and Dynamic Behaviours

16:30 Poster Session

18:00 Welcome Reception19:3021:00

TuesdayOctober 10

Pacifico Yokohama Pan PacificHotel1F Main Hall 4F 5F Sub Hall 1 5F Sub Hall 2

9:00

Poster Display

9:30 P5Stephen Oliver

10:00 Break10:30 S2a

Cardiovascular Systems BiologyS2b

Yeast Systems BiologyS2e

Network Biology

12:30 Lunch Lunch Lunch14:00 S2d

Systems ImmunologyS2c

Metabolomics and BioprocessS2f

Student Session

16:30 Poster Session

18:3019:00 Banquet21:00

WednesdayOctober 11

Pacifico Yokohama1F Main Hall 4F 5F Sub Hall 1 5F Sub Hall 2

9:15 S3aSystems Biology of Diabetes

S3bDevelopmental Systems Biology

S3cComplex Systems Biology

10:30 Break11:00 S3d

Cancer Systems BiologyS3e

Systems Neurobiology

S3fControl and System Theory for

Systems Biology12:30 Lunch14:00 S3g

Synthetic BiologyS3h

Signal Transduction

S3iNovel computational environments

for systems biology16:30 Break17:00 Panel Discussion

Closing18:00

ThursdayOctober 12

Miraikan AISTMiraikan Hall Meeting Room 1 Meeting Room 2 Meeting Room

Synthetic BiologySystems Biology and the Human

Health Risks of EnvironmentalChemicals

SBML Forum RTK Workshop

FridayOctober 13

Miraikan AISTMiraikan Hall Meeting Room 1 Meeting Room 2 Meeting Room

SBML Forum RTK Workshop

Tutorial

Conference

Workshop

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Student Session

Venue: Pacifico Yokohama, 5F Sub Hall 2Date: Tuesday, October 10, 2006, 14:00-16:30

Chair: Marc Vidal, Dana-Farber Cancer Institute

SpeakersThe following Speakers will give an oral presentation on their Posters. These Speakers' posters were selected by the Student Session Review Committee as the best poster abstracts submitted in the Student Category.

MAPK signaling network properties giving rise to specific cellular fate decisions (BS24)Silvia Santos, Philippe BastiaensEMBL

Applied genome-scale modelling of Aspergillus niger (FI58)Mikael Andersen, Michael L. Nielsen, Jens NielsenTechnical University of Denmark

Regulatory Dynamics of Synthetic Gene Networks with Positive Feedback (FS06)Yusuke Maeda, Masaki SanoThe University of Tokyo

Monitoring MAPK osmo-signaling in individual yeast cells (BS09)Dale Muzzey, Carlos Gomez-Uribe, Jerome Mettetal, Alexander van OudenaardenMIT-Harvard

Mathematical modelling of the role of HIF-1 in tumour growth (FN27)Alexander Fletcher, Jonathan Chapman, Christopher BrewardUniversity of Oxford

Study of Dependency of Synchronization of Beta-cells Insulin Secretion on Size of Langerhans Islets (MD04)Ariosto Silva, Jose YunesCentro Infantil Boldrini

The following scientists reviewed the abstracts for the Student Session:- Hsuan-Cheng Huang, National Yang-Ming University, Taiwan- Bruce Shapiro, California Institute of Technology- Tau Mu Yi, UCI- Upinder Bhalla, National Centre for Biological Sciences, Bangalore, India- Marie Csete, Emory University School of Medicine- Martin Robert, Keio University

Organizers:Satya Arjunan, Keio UniversityJohn Cumbers, Brown University

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P1 10:00-10:30, October 9 Main HallElectricity meets chemistry: fast and slow signaling in memoryUpinder S. BhallaNational Centre for Biological Sciences, TIFR, Bangalore, IndiaContacts: bhalla@ncbs.res.in

Deliberations on memory mechanisms often seem to proceed on at least three independent tracks. One of these involves biochemical mechanisms for plasticity, including feedback loops and cellular activation. Space is another dimension, and is the arena for interactions between synapses, and propagation of signals between synapses, dendrites, and the cell body. Finally, electrical activity is a function of cell as well as network dynamics, and here too feedback may play a role through reverberating activity in network loops. It is an interesting process to develop models that impinge on all of these levels, because of the wide range of timescales, numerical techniques, and sheer computational load. It is especially tricky to get parameters for such models. I will describe a study where we have used coupled electrical and biochemical compartmental modeling, and weeded out several candidate models by comparing their predictions to our experiments. The surviving models incorporate chemical, spatial and electrical ingredients. They exhibit network-activity controlled single-cell reverberating activation, with interesting spatial consequences. We suggest that this is a form of short-term and spatially defined memory. It sits at the interface between individual synapses and dendrites, and also between network and cellular attributes of memory.

http://www.ncbs.res.in/~bhalla/index.html

P2 10:30-11:00, October 9 Main HallSpatio-temporal patterns of intracellular signalingAtsushi MiyawakiRIKEN Brain Science InstituteContacts: matsushi@brain.riken.go.jp

"Why bio-imaging, i.e. real time fluorescence imaging?" Currently, this is a topic of great interest in the bioscience community. Many molecules involved in signal transduction have been identified, and the hierarchy among those molecules has also been elucidated. It is not uncommon to see a signal transduction diagram in which arrows are used to link molecules to show enzyme reactions and intermolecular interactions. To obtain a further understanding of a signal transduction system, however, the diagram must contain the three axes in space as well as a fourth dimension, time, because all events are controlled ingeniously in space and time. Since the isolation of green fluorescent protein (GFP) from the bioluminescent jellyfish in 1992 and later with its relatives, researchers have been awaiting the development of a tool, which enables the direct visualization of biological functions. This has been increasingly enhanced by the marriage of GFP with fluorescence resonance energy transfer (FRET) or fluorescence cross-correlation spectroscopy (FCCS), and is further expanded upon by the need for "post-genomic analyses." It is not my intent to discourage the trend seeking the visualization of biological function. I would like to propose that it is time to evaluate the true asset of "bio-imaging" for its potential and limitations in order to utilize and truly benefit from this novel technique.

http://www.brain.riken.go.jp/english/b_rear/b5_lob/a_miyawaki.html

P3 11:30-12:00, October 9 Main HallBiological large scale integrationStephen QuakeDept of Bioengineering and (by courtesy) Applied Physics, Stanford University and Howard Hughes Medical InstituteContacts: quake@stanford.edu

The integrated circuit revolution changed our lives by automating computational tasks on a grand scale. My group has been asking whether a similar revolution could be enabled by automating biological tasks. To that end, we have developed a method of fabricating very small plumbing devices – chips with small channels and valves that manipulate fluids containing biological molecules and cells, instead of the more familiar chips with wires and transistors that manipulate electrons. Using this technology, we have fabricated chips that have thousands of valves in an area of one square inch. We are using these chips in applications ranging from bioreactors to structural genomics to systems biology. However, there is also a substantial amount of basic physics to explore with these systems – the properties of fluids change dramatically as the working volume is scaled from milliliters to nanoliters!

http://med.stanford.edu/profiles/Stephen_Quake/

Plenary Talk AbstractsSession Abstracts

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P4 12:00-12:30, October 9 Main HallEvolvability and hierarchy in rewired bacterial gene networksLuis Serrano1,2, Mark Isalan*1, Caroline Lemerle2, Konstantinos Michalodimitrakis2, Barbara Di Ventura2, Pedro Beltrao2, Carsten Horn2 and Emanuele Raineri2

1. EMBL-CRG Systems Biology Programme, Centre for Genomic Regulation, Spain2. EMBL, Germany*Contacts: mark.isalan@crg.es

Bacterial gene networks are highly plastic, allowing radical reconnections at the summit of the gene network hierarchy, fuelling evolvability.Sequencing of genetic material from several organisms has revealed that duplication and drift of existing genes has primarily molded the contents of a given genome. Though the effect of knocking out or over-expressing a particular gene has been studied in many organisms, no study has systematically explored the effect of adding new links in a biological network. To explore network plasticity, we constructed 598 recombinations of promoters (including regulatory regions) with different transcription or s-factors in Escherichia coli, over the genetic background of the wild-type. We found that ~95% of reconnected networks are tolerated by the bacterial cell and very few give different growth profiles. Expression levels correlate with the position of the factor in the wild-type network hierarchy. Most importantly, we find that certain combinations consistently survive over the wild-type under various selection pressures. This suggests that new links in the network could readily confer a fitness advantage to individuals in a population and hence may fuel evolution.

http://www-db.embl.de/jss/EmblGroupsHD/per_397.html

P5 9:30-10:00, October 10 Main HallDealing with the complexity of a ‘simple’ eukaryotic cell.Stephen G. OliverFaculty of Life Sciences, The University of Manchester, U.K.Contacts: steve.oliver@manchester.ac.uk

Systems biology aims at taking a more synthetic or holistic approach to deciphering the workings of living organisms. Although the ultimate aim is to construct mathematical models of complete cells or organisms that have both explanatory and predictive power, we are some way from achieving such global syntheses and we need a principled way of reducing the complexity of the problem. Accordingly, we require a top-down strategy to provide an initial coarse-grained model of the cell, and a bottom-up strategy in which individual sub-systems are modeled.Metabolic Control Analysis (MCA) is a conceptual and mathematical formalism that models the relative contributions of individual effectors in a pathway to both the flux through the pathway and the concentrations of individual intermediates within it. To exploit MCA in an initial top-down systems analysis of the eukaryotic cell, two categories of experiments are required. In category 1 experiments, flux is changed and the impact on the levels of the direct and indirect products of gene action is measured. We have measured the impact of changing the flux on the transcriptome, proteome, and metabolome of Saccharomyces cerevisiae. In this whole-cell analysis, flux equates to growth rate. In category 2 experiments, the levels of individual gene products are altered, and the impact on the flux is measured. We have used competition analyses between the complete set of heterozygous yeast deletion mutants to reveal genes encoding proteins with high flux control coefficients. For the bottom-up approach, the initial problem is one of systems identification. While a lot of time is currently spent debating the question “What is Systems Biology?”, why (in an organism where we know so much about its biochemistry, physiology, and cell biology as S. cerevisiae) should it be a problem to identify the biological sub-systems that must be fully characterised and built into a comprehensive model of the eukaryotic cell? This problem arises because we have previously studied these biological systems in isolation and in a rigorously reductionist fashion. Now, we must study them as parts of an integrated whole. The problem is that our current view of, say, a metabolic or signal transduction pathway is often two-dimensional (rather than four-dimensional) and is frequently poorly integrated, if at all, with other cellular pathways. Thus our view of the network of metabolic pathways may not be the same as the yeast’s. In order to gain a “yeast’s eye view”, we have coupled flux balance analysis with both metabolomics and genetics. Although the initial aim of these approaches is the identification of the ‘natural’ metabolic systems of yeast, the principles involved should be more widely applicable to the problem of biological systems identification.

http://www.ls.manchester.ac.uk/people/profile/index.asp?tb=0

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I S1a SYSTEMS BIOLOGY FOR MEDICINE 14:00-16:00, October 9

Systems Biology for Drug Discovery Main HallS1a-1 From molecular events to clinical outcome: computational systems biology in the pharmaceutical

industry Klaus Prank GlaxoSmithKline

S1a-2 Harnessing systems biology using chemical synergies Joseph Lehár Computational Biology, CombinatoRx Inc, Cambridge MA, Bioinformatics, Boston University Contacts: jlehar@combinatorx.com

Combination drugs can overcome compensatory mechanisms or evolved resistance by attacking disease on several fronts, and also provide a new window on biological systems. We present simulations and experiments that show the relationship between chemical synergies and target connectivity, as well as preliminary results from combination screens of targeted agents in yeast and tumor cell lines.Despite the success of discovery efforts focused on specific targets, many drugs are less effective than expected [Sams-Dodd 2005], due to mechanistic complexity [Hartwell 2001] or evolved resistance. Network simulations [Csermely 2005] and clinical oncology [Kaelin 2005] suggest that disease is more controllable through multi-target approaches, and indeed combinations are the norm for cancer and many infectious diseases. CombinatoRx is systematically screening combinations of approved drugs in cellular disease models [Borisy 2003], to find synergies that can be optimized towards novel combination drugs.We show that chemical combinations can also yield connectivity information through their response surface shapes. Pathway simulations with pairs of inhibitors produce distinct responses depending on how the targets are connected. The predicted shapes are reproduced in a yeast experiment, with further support from screens using human cells. While analogous to genetic interactions [Tong 2003], chemical synergies provide complementary and more detailed information for network models about connections between their protein targets. Chemicals can also be efficiently screened in disease models that are not amenable to genetic studies. We also present preliminary results from screens testing combinations of ~100 chemical probes with known targets using yeast and tumor cell lines. The experiments are designed to improve our understanding of yeast networks, and to identify new multi-target mechanisms with therapeutic potential for cancer.

http://users.rcn.com/lehar

S1a-3 Application of systems biology for pharmaceutical drug development Jeff Trimmer Entelos Inc.

S1a-4 Systems biology in drug discovery and development: impact and challenges Didier Scherrer AstraZeneca

S1a-5 Technological breakthrough for cell-based target discovery Masato Miyake CytoPathfinder, Inc. Contacts: masato.miyake@cytopathfinder.com

Strategy to identify new and right targets at early stage of drug discovery has long been discussed to improve the R&D productivity. Genome-wide target screening and target combination finding are growing as new waves of cell-based target discovery on the background of emerged antibodies, aptamers, and nucleic acid medicines. The experimental scale of the cell-based screening is getting larger year by year for successful target discovery. Therefore, high-throughput screening and data management & integration technologies are rapidly growing. On the other sides, technologies to select right targets are studied in cell biology. Various technologies such as stem cell differentiation, cell separation, immortalization, xenografts, etc. are used to establish in vitro models (cells and markers) which correlate to clinical data. However the culture scale of reliable in vitro model is still small in general. The experimental scale gap between new target discovery and right target discovery may be pointed out as technological innovation needs. Here, we introduce Transfection microarray (TMA), which is a microarray for highly paralleled cell transfection. By using TMA, large-scale functional screening of cDNAs / siRNAs is operated in the small culture. We may show the TMA-based strategy to identify new and right targets at early stage of drug R&D.

http://www.cytopathfinder.com

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I S2a SYSTEMS BIOLOGY FOR MEDICINE 10:30-12:30, October 10

Cardiovascular Systems Biology Main HallS2a-1 Cardiac systems biology Andrew McCulloch1, Jacob Feala1, Sarah Flaim1, Roy Kerckhoffs1, Giovanni Paternostro2, Jeffrey Saucerman3

1Department of Bioengineering, University of California, San Diego, La Jolla, CA, 2The Burnham Institute, La Jolla, CA, 3Department of Biomedical Engineering, University of Virginia, Charlottesville, VA

Computational models of the heart can be integrative in several important ways. First, they permit information integration of genome scale data sets that would otherwise be difficult to interpret and understand. We illustrate this in the analysis of high-throughput phenotypic and metabonomic data on cardiac function in the fruitfly drosophila melanogaster. We use drosophila as a model organism for studying cardiac aging and hypoxia tolerance, and integrating these data with constrain-based metabolic models built in large part with data from the Kyoto Encyclopedia of Genes and Genomes (KEGG). Systems models of cardiac myocytes achieve functional integration, by predicting how the functions of individual network components combine to give rise to physiological functions. We illustrate this with our recent models of β-adrenergic regulation of myocyte excitation-contraction coupling. Multi-scale computational models aim to achieve structural integration across physical scales of biomedical organization from molecule to organize. We illustrate this with examples from our recent research on arrhythmia mechanisms in genetic disease and the effects of external interventions such as pacing and pericardiectomy on ventricular-vascular coupling in vivo.

http://cmrg.ucsd.edu

S2a-2 Kyoto model, a comprehensive cardiac cell model Akinori Noma, Satoshi Matsuoka and Nobuaki Sarai Cell/Biodynamics Simulation Project Kyoto University, Department of Physiology, Faculty of Medicine Kyoto University, Japan Contacts: noma@card.med.kyoto-u.ac.jp

The magnitude and time course of developed tension is regulated by multiple functional units, such as [Ca2+]i, molecular machinery

of contraction, membrane excitation, ion homeostasis within the cell, excitation-contraction coupling, neural regulation, cell volume regulation and energy metabolism in cardiac myocytes. So far, a huge amount of experimental findings on each issue has been accumulated, and it is possible to develop a comprehensive cardiac cell model to analyze the interactions of many molecular functional units underlying the regulation of the cardiac contraction. Starting from the models of cardiac membrane excitation (1), we developed a comprehensive cell model, Kyoto Model (2). Kyoto model can respond to various experimental interventions in a reversible manner. Increasing [Ca2+]

o results in a positive inotropy accompanied with the slight shortening of the action potential

duration. Decreasing [Na+]o increases the force of contraction through the accumulation of Ca2+ within the sarcoplasmic reticulum

by modulating the Na/Ca exchange. Varying [K+]o affects both the action potential shape and the resting membrane potential. The

force of contraction increases with decreasing [K+]o. The Ca2+ stored within the sarcoplasmic reticulum (2~4 mM) is released by

the activation of the RyR channel through the influx of Ca2+ via L-type Ca2+ channels. [Ca2+]i is determined by the intracellular Ca2+

buffer as well as the binding to troponin C. The contraction model is based on the Negroni and Lascano (2001), but is improved for the positive cooperativity for Ca2+-mediated activation by combining with the model of Robinson et al (2002). The ATP homeostasis is established between the consumption by the myofilament, Na/K pump and SERCA and the production by mitochondria. Removing oxygen results in shortening of the action potential and loss of contraction. Quantitative dynamic computer models, which integrate a variety of molecular functions into a cell model, provide a powerful tool to create and test working hypotheses. Our new modeling tool, the simBio package (freely available from http://www.sim-bio.org/) is used for constructing cell models such as cardiac cells, epithelial cells and pancreatic β cells. The simBio package is written in Java, uses XML and solves ordinary differential equations.1) DiFrancesco, D., Noble, D., 1985. Philos. Trans. R. Soc. Lond. B Biol. Sci. 307:353-398.2) Matsuoka S., Sarai N., Jo H., and Noma A. 2004 Prog. Biophys. Mol. Biol. 85:279-299.3) Negroni, J. A., Lascano, E.C. 1999. J.Mol.Cell.Cardiol. 31: 1509-1526.4) Robinson JM., Wang Y., Kerrick GL., Kawai R., and Cheung HC. 2002 J. Mol. Biol. 322:1065-1088.http://www.card.med.kyoto-u.ac.jp

S2a-3 Cardiomyopathy in mice and men Jonathan Seidman Harvard Medical School

Hypertrophic cardiomyopathy (HCM), caused by missense mutations in sarcomere protein genes, increases left ventricular wall thickness, susceptibility to cardiac arrhythmias and sudden cardiac death. Cardiac tissue from affected individuals demonstrate fibrosis, myocyte disarray and myocyte hypertrophy. Disorganized cell-cell contact (myocyte disarray) and cardiac fibrosis, prototypic but protean features of HCM histopathology, are suggested as potential triggers for ventricular arrhythmias that lead to sudden death. We have studied the epidemiology of left ventricular hypertrophy and have demonstrated that rare sarcomere protein gene mutations account for more than 50% of unexplained in young and middle aged, while other causes may account for most hypertrophy in the elderly.The mechanisms by which sarcomere protein gene mutations lead to unexplained hypertrophy are being investigated in mouse models of this disease. Rigorous assessment of whether these factors increase arrhythmia vulnerability in humans is difficult due to limited

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myocardial tissue access and confounding variables including genetically heterogeneous HCM mutations, background genotypes and lifestyles. We report electrophysiological studies and comprehensive myocardial histopathologic analyses of mice engineered to carry an HCM mutation. Genetically inbred HCM mice had remarkably inhomogeneous histopathology and susceptibility to arrhythmias. Among inbred HCM mice, neither the extent nor distribution of myocyte disarray or cardiac fibrosis correlated with abnormalities in ex vivo signal conduction properties or in vivo electrophysiological properties. In contrast, increased ventricular hypertrophy significantly increased arrhythmia susceptibility. These data indicate that somatic responses to a sarcomere gene mutation account for variable HCM histopathology and demonstrate that myocyte hypertrophy more than fibrosis or disarray correlates with arrhythmic risk. Independent somatic triggers appear to stimulate fibrosis, and myocyte disarray. A shared factor activates cardiac hypertrophy and arrhythmias. Presumably each of these separate factors activates a distinct pathway that stimulates different responses to sarcomere protein gene mutations.

http://genetics.med.harvard.edu/~seidman/

S2a-4 Direct observation of transcription in the human cell using tiling array Tatsuhiko Kodama The University of Tokyo

Sequential gene expression upon stimulation is a key cellular mechanism for adaptation, and temporal analysis of transcriptional activation by TNFa-nuclear factor kappa B, nuclear receptors and p53 indicate that oscillating activation may be an important mechanism to generate a temporal cascade. Transcription of pre-mRNA in the human cell is coupled with its processing and selective degradation. Observation of this complex process is hampered by an interruption of coding sequence by a large non-coding intorns. Oligonucleotide tiling array covering whole genome sequence has been developed to obtain higher resolution of gene expression,. As compared with exon RNA, intron RNA is degraded rapidly during splicing, and may be useful tool to monitor the rate of transcriptional activation. Here we report that first wave of oscillating expression of intron RNA and its processing can be monitored using tiling array with high temporal resolution (7.5min). We selected 100 genes induced by TNFa and designed tiling array monitoring pre-mRNAs of these gene loci. First wave of oscillating expression was monitored in 4 large gene loci (>100kb) and average speed of transcriptional elongation was 3.2kb/min, which is faster than previously reported value without measureing the oscillation (1.2-24kb/min). Temporal analysis of transcription using tiling arrays will be a useful tool analyzing the transcription and processing.

http://www.lsbm.org

I S2d SYSTEMS BIOLOGY FOR MEDICINE 14:00-16:30, October 10

Systems Immunology Main HallS2d-1 Evolution and divergence of herpesviral protein interaction networks Even Fossum*1, Armin Baiker*1, Caroline C. Friedel2, Silpa Suthram3, Seesandra V. Rajagopala4, Björn Titz4, Tina Schmidt5, Theo Kraus1, Sourav Bandyopadhyay3, Dietlinde Rose1, Mareike Uhlmann1, Christine Zeretzke1,

Yu-An Dong2, Hélène Boulet1, Susanne M. Bailer5,Ulrich Koszinowski1, Trey Ideker6, Peter Uetz4, Ralf Zimmer2

and Jürgen Haas1

1Max-von-Pettenkofer Institut, LMU München, 2Institut für Informatik, LMU München, 3Program in Bioinformatics, University of California San Diego, 4Institut für Genetik, Forschungszentrum Karlsruhe , 5Institut für Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, Homburg, 6Department of Bioengineering, University of California San Diego

Contacts: haas@lmb.uni-muenchen.de

Herpesviruses are a family of large DNA viruses widely spread in vertebrates which cause a variety of different diseases in animals and man. We performed a comprehensive yeast-two-hybrid analysis of intraviral protein interactions in five different species of the herpesvirus family: Herpes simplex virus 1 (HSV-1), Varicella zoster virus (VZV), murine Cytomegalovirus (mCMV), Epstein-Barr virus (EBV) and Kaposi’s sarcoma associated herpesvirus (KSHV) revealing 1,252 interactions including 231 interactions between 41 core ortholog proteins. Whereas previous studies compared species that had been analysed in different laboratories by various methods, we explored 5 different species using exactly the same protocols. Nevertheless, at first glance there was little overlap between the networks of the five herpesvirus species, similar to previous Y2H datasets of different cellular networks. The general network topology was similar in all herpesviral networks: the degree distribution differed from cellular networks (if a power law distribution is approximated the power coefficient is considerably lower in comparison to cellular networks) and showed no high local clustering as in small-world networks1. Moreover, herpesviral networks could not be subdivided into distinct functional submodules or complexes, which appears to be an inherent characteristic of large cellular networks such as that of yeast and human. Co-immunoprecipitation experiments indicated that the majority of interactions is conserved between core orthologs and demonstrated that protein function can be conserved without sequence homology. In contrast, the network outside the common core is either species- or subfamily-specific, reflecting distinct functional properties of these proteins. Whereas the five species were equidistant based on their core interaction networks, the analysis of the complete viral networks yielded a phylogeny that was consistent with the known evolutionary relationships between the alpha, beta, and gamma subfamilies. Our study provides evidence that protein interactions and network structures constitute adaptive evolutionary traits and can thus be used to assign phylogenetic relationships.

http://www.baygene.de/pro-engl-3_1a.htm

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S2d-2 Pathway biology approach to the interferon system Peter Ghazal University of Edinburgh Medical School

Interferons (IFNs) play a pivotal role in innate and adaptive immunity against infection. Here, we present a systematized interpretation and analysis of the IFN pathway based on a research synthesis review of 257 nodes in the network. The relationships of the components were graphically notated as a consensus logic interaction diagram. Topological characterisation of the constructed pathway showed network features consistent with a scale-free connectivity and systems robustness with predicted flexibility for a number of different states. A genetic network of 56 genes and 100 edges from the consensus diagram was used for analysis of gene expression data obtained by profiling primary mouse macrophages treated with IFNγ and/or infected with murine cytomegalovirus. Statistical and simulation analyses showed the expression changes mapped to discrete and specific sub-systems of the IFN pathway, indicative of pro-inflammatory and anti-viral functions. Notably, IFNγ co-stimulation of infected cells results in the dominance of IFNγ over the viral specific sub-network. These results reveal for the first time discrete states of sub-system activity of the IFN pathway and represent a systematic methodology for constructing and exploiting biological pathways in general.

S2d-3 The center for inflammation and regenerative medicine: a service model Gilles Clermont The University of Pittsburgh Contacts: cler@PITT.EDU

The University of Pittsburgh Medical Center is a large tertiary care center hosting more than 130 intensive care unit beds, is the largest solid organ transplant, and hosts the McGowan Institute dedicated to regenerative medicine. Systems modeling of inflammation, the crucial pathophysiologic process determining outcome in the critically ill patient, is a prime focus of interest of a team including clinicians, biologists, mathematicians, engineers and computer scientists. This interdisciplinary team has created the Center for Inflammation and Regenerative Medicine, which seeks to (1) offer transdisplinary expertise to academic and corporate researchers interested in the analysis and modeling of complex datasets, (2) train a new generation of scientists in translational systems biology and (3) promote scientific diffusion of the relevance of an integrative approach to patient care and the development of therapies.

www.mirm.pitt.edu/cirm

www.scai-med.org www.pittsburghcomplexity.net www.iccai.org

S2d-4 To kill or not to kill - decision making in natural killer cells Roland Eils1,3, Sven Mesecke1, Doris Urlaub2, Hauke Busch1, Carsten Watzl2

1Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany; 2Institute for Immunology, University of Heidelberg, Germany; 3Department for Bioinformatics and Functional Genomics, Institute for Pharmacy and Molecular Biotechnology, University of Heidelberg, Germany

Contacts: r.eils@dkfz.de

The immune system is essential in the protection of the host against a variety of infectious agents and the growth of transformed cells. Natural Killer (NK) cells are at the junction of the innate and the adaptive immune response and are important in the fight against viral infections and cancer. The effector functions of NK cells are controlled by a balance of positive and negative signals that are transmitted via various kinds of surface receptors. Inhibitory receptors guarantee the tolerance of NK cells towards target cells with normal MHC class I expression. Loss of this expression, e.g. during viral infection or transformation, reduces the inhibitory signal, and enables stimulatory surface receptors to shift the balance towards activation and subsequent killing of a locally attached target cell. To date our understanding about the integration of positive and negative signals and the decision making process inside NK cells remains poor. Here, we propose a mechanism by which NK cells first integrate antagonising signals and then compute a reliable killing decision. Predictions derived from this mechanistic model are tested experimentally and will be compared with established knowledge. This proposed mechanism of NK cell regulation enables a novel insight into the decision making process during lymphocyte activation. It can serve as basis for any future manipulation of NK cell function to enhance the anti-tumour activity of these important immune cells.

http://www.dkfz.de/tbi

S2d-5 Stem cells and pain: linking immunity to regeneration Marie Csete Emory/GaTech Human Embryonic Stem Cell Core Contacts: marie.csete@emoryhealthcare.org

Pain is experienced by all people, yet is poorly understood and often poorly treated. In particular many traumatic or degenerative disease processes (for which stem cell therapies are being studied) are complicated by pain. In this way, pain is part of normal regeneration, yet the role of stem cells in treating pain has not been explored. Pain can be broadly divided into nociceptive

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(appropriate to the stimulus) and neuropathic (inappropriate severe and long-lasting) types. We used an animal model of neuropathic pain, chronic constriction injury of the rat sciatic nerve, to study the potential of stem cells for pain therapy. Our data show that infusion of bone marrow mononuclear cells containing a mixed stem cell population after the injury, results in reversal of pain behaviors 10 days later, whereas untreated control rats remain in pain. Several possible mechanisms for pain reversal by bone marrow transplant will be discussed including modulation of immune cell infiltrates, neurotrophic factor signaling (particularly erythropoietin and GDNF), vasodilatation, elaboration of heat shock proteins, and regeneration of Schwann and vascular cells. This work suggests that stem cells modulate pain signals as part of their regenerative roles, and serve as a link to the nervous system after injury.

http://userwww.service.emory.edu/~mcsete

I S3a SYSTEMS BIOLOGY FOR MEDICINE 9:15-10:30, October 11

Systems Biology of Diabetes (Novo Nordisk-sponsored) Main HallS3a-1 Understanding diabetes pathogenesis: the need for systems biology Pierre De Meyts Receptor Systems Biology Laboratory, Hagedorn Research Institute, Gentofte, Denmark Contacts: pdm@hagedorn.dk

The two major forms of diabetes mellitus, type 1 and type 2 diabetes, are both complex diseases of poorly understood pathogenesis. The poor understanding of molecular mechanisms underlying pathogenesis results in a penury of effective drug therapies. Type 1 diabetes results from progressive beta cell destruction by incompletely defined autoimmune processes. Insulin treatment is an absolute requirement to prevent death from ketoacidosis. Type 2 diabetes is a complex disease which is reaching epidemic proportions due a combination of lifestyle factors that favor obesity, and genetic and environmental factors. The pathogenesis of type 2 diabetes involves alterations in insulin production and secretion by the pancreatic beta cells, as well as disturbances in the target cells sensitivity to insulin action. Reductionist approaches have failed to unravel the complex interactions between transcriptional networks that regulate beta cell development and differentiated function, and the signal transduction mechanisms in both beta cells and insulin target tissues, the combined disturbance of which results in impaired metabolic homeostasis. A systems biology approach is clearly warranted.

S3a-2 A systems biology approach to type 1 diabetes Allan E. Karlsen1,2, Jørn Nerup2 & Flemming Pociot2

1Insulin, Incretin and Islet Biology, Novo Nordisk A/S, 2Steno Diabetes Center, Denmark Contacts: aek@novonordisk.com

Type 1 diabetes mellitus (T1D) is the result of an autoimmune associated destruction of the beta-cells in the islets of Langerhans in the pancreas. The pathogenesis of T1D is accompanied by infiltration of the islets with auto-reactive lymphocytes and macrophages (insulitis), releasing a cocktail of cytokines of which especially interleukin-1β is specifically toxic to the beta-cells in the islets.We have combined transcriptome and proteome analysis of different in vitro and in vivo models of T1D to elucidate the mechanisms behind cytokine and immune mediated beta-cell destruction.The results have identified a number of proteins, that when over-expressed in beta-cells influence their response to cytokines. Combining this information with data from our genetic studies in a systems biology approach supports the hypothesis that spontaneous and cytokine induced beta-cell destruction is caused by complex, intracellular protein – protein or protein/DNA interactions, ”controlled” at the level of expression by common alleles (polymorphisms) of normal genes in unfavourable combinations. Thus, a battle between protective and deleterious effects in the beta-cells determines the outcome. Knowledge about the underlying mechanisms may provide novel targets for future pharmacological and/or genetic intervention in the beta-cell destructive processes in diabetes.

http://www.novonordisk.com

S3a-3 The transcriptome as a window into pathogenesis of type 1 diabetes Nathan Goodman, Burak Kutlu Institute for Systems Biology natg@shore.net

We have generated a comprehensive atlas of genes expressed in beta cells, islets, and related cell types and lines by combining data from MPSS analysis and array studies. We find around 9800 genes expressed consistently in human islets regardless of individual variation. Slightly more genes are expressed in exocrine tissue, 11200, duct cells have around 4000, and rat beta cells and insulin-producing cell lines have around 7500. Due to technical difficulties, it is impossible to isolate human beta cells, but based on computational analysis, we have determined a core list of 2025 and 860 genes that are enriched in human islets and beta cells, respectively. We are also studying the dynamics of cytokine-induced beta cell destruction by microarray and qPCR analysis. Results from arrays show 1057 genes are differentially expressed over a period of 96h IL1+IFN exposure. Chemokines, NF-kB and JAK-STAT signaling pathways are dramatically activated. Our approach mainly relies on integrating and comparing observations from different species

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and publicly available pathway and interaction data. Comparison with similar experiments in rodents points reveals many similarities, however with delayed behavior in human cells. The time series will hopefully help us draw casual relationships between the activated pathways and beta cell death.

http://T1DBase.org

I S3d SYSTEMS BIOLOGY FOR MEDICINE 11:00-12:30, October 11

Cancer Systems Biology Main HallS3d-1 Design Principles of the JAK-STAT Signaling Pathway Ursula Klingmueller Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ)

Growth and differentiation processes are regulated by complex intracellular signaling networks. In many cancer cells signaling through the JAK-STAT or the SMAD signaling pathways are altered. To identify general principles how these pathways influence cellular decisions and to predict targets for intervention we are combining quantitative data generation with mathematical modeling. We applied quantitative immunoblotting to monitor the interleukin (IL)-6 induced activation of gp130, JAK1 and STAT3 in primary hepatocytes. The time-resolved experimental data could only be fitted at sufficient quality by a mathematical model capturing the possibility that STAT3 cycles between the nucleus and the cytoplasm. Although it has been demonstrated that SMAD2 cycles between the cytoplasm and the nucleus it was not possible to fit time resolved data for transforming growth factor (TGFbeta) induced SMAD2 phosphorylation in in primary hepatocytes by a simple cycling model. We had to include a negative feedback loop and experimentally verified a critical role for the oncoprotein SnoN. Thus, by dynamic pathway modeling rapid nuclear-cytoplasmic cycling could be identified as a general building principle of signaling cascades that make use of latent transcription factors and rapidly mediate signal transmission from the cell surface to the nucleus.

www.dkfz.de/de/systembiologie/index.html

S3d-2 Predicting the outcome of chemotherapy through pathway modelling Charles Auffray CNRS and Pierre & Marie Curie University – Villejuif, France Contacts: charles.auffray@vjf.cnrs.fr

The molecular mechanisms underlying innate tumor drug resistance to cancer therapy remain poorly understood, as molecular studies have focused on drug-selected tumor cell lines or individual candidate genes using samples derived from patients already treated with drugs. Transcriptional profiles of clinical samples collected from colorectal patients prior to their exposure to a combined chemotherapy were established using microarrays. Vigilant experimental design, power simulations and robust statistics allowed successful discrimination, for the first time prior to drug exposure, of subsequently diagnosed chemo-sensitive and resistant patients, based on the expression profile of 679 genes. Functional annotation, ontology enrichment analysis and pathway modelling using CellDesigner provided a unique representation of the cellular states underlying drug responses. It forms a solid foundation for a system-level analysis of the molecular interaction networks involved, and for the design of by-pass chemotherapy schemes allowing critical therapeutic intervention. In addition, through multivariate analysis and cross validation, powerful predictors of the response to chemotherapy were developed.Graudens et al. Deciphering cellular states of innate tumor drug responses. (2006) Genome Biology 7:R19

http://genomebiology.com/2006/7/3/R19

S3d-3 From simulation to therapy: a systems biology approach to oncogene detection Avijit Ghosh Drexel University Contacts: avijit@physics.drexel.edu

Activation of the Extracellular signal Regulated Kinases (ERK1/2; p42/p44 MAPK) is one of the most extensively studied signaling pathways, not least because it occurs downstream of oncogenic RAS. We take advantage of the wealth of experimental data available on the canonical RAS/ RAF/ MEK/ ERK pathway of Bhalla et. al. to test the utility of a newly developed nonlinear analysis algorithm designed to predict likelihood of cellular transformation. By using ERK phosphorylation as an "output signal", the method analyzes experimentally determined kinetic data and predicts putative oncogenes and tumor suppressor gene products impacting the RAS/ MAPK module using a purely theoretical approach. This analysis identifies several modifiers of ERK/ MAPK activation described previously. In addition, several novel enzymes are identified which are not previously described to affect ERK/ MAPK phosphorylation. We have extended this method to study disparate pair mutations in enzyme/protein interactions and in expression levels in signal transduction pathways and have applied it to the MAPK signaling pathway to study how synergistic or cooperative mutations in signaling networks act together to cause malignant transformation.The set of in silico transformed cells designed in this manner have been subject to a series of virtual drugs designated by a binding

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affinity kd and concentration. A map of best targets within the pathway can be quantitated and furthermore ranked. Among the highly

ranked targets are several well known in the literature such as the Ras inhibitors. Several novel targets are also highly ranked. In addition, the analysis points to the use of Calcium blockers, not currently used in cancer therapy, as a possible avenue for therapeutic intervention.

II S1b SYSTEMS BIOLOGY OF BASIC BIOLOGICAL SYSTEMS 14:00-16:00, October 9

Cyclic and Dynamic Behaviours 5FS1b-1 A generic model of cell cycle regulation in eukaryotes John J. Tyson, Attila Csikasz-Nagy, Katherine C. Chen, and Bela Novak Department of Biological Sciences, Virginia Polytechnic Institute & State University, USA, and Department of Agricultural

Chemical Technology, Budapest University of Technology & Economics, Hungary Contacts: tyson@vt.edu

The protein interaction network regulating DNA synthesis and mitosis seems to be universal among eukaryotic cells. The idiosyncrasies of cell cycle regulation in particular organisms are attributable to specific settings of the rate constants in the dynamical network, and these settings are determined ultimately by the genetic makeup of an organism. Alternative parameter settings are known for fission yeast, budding yeast, early embryos of frog and fruit fly, and for mammalian cells in culture. Generic properties of the model are revealed by one-parameter bifurcation diagrams, which show (1) how cell growth drives progression through the cell cycle, (2) how cell size homeostasis may be achieved (3) how cell cycle checkpoints operate, and (4) how mutations alter the way cells grow and divide. Two-parameter bifurcation diagrams compactly summarize the dependence of cell phenotype on gene dosage. This theoretical framework reveals both the universality and particularity of cell cycle regulation and facilitates construction, in modular fashion, of increasingly complex models of the networks controlling cell growth and division.Ref. Csikasz-Nagy, Battogtokh, Chen, Novak & Tyson (2006) Biophys J 90:4361-79This research is supported, in part, by the Defense Advanced Research Project Agency (USA), the James S. McDonnell Foundation (USA), and COMBIO (EU).

http://mpf.biol.vt.edu/

S1b-2 Probing structure and dynamics of cell cycle in budding yeast Lilia Alberghina#, Matteo Barberis# *, Marco Vanoni #, Edda Klipp* #Dept. of Biotechnology and Biosciences - University of Milano-Bicocca - Milano, Italy, *Max-Planck Institute for Molecular

Genetics - Berlin Center for Genome based Bioinformatics (BCB) - Berlin, Germany Contacts: lilia.alberghina@unimib.it

The construction of a novel mathematical model of the G1 to S transition is reported. It accounts both for literature findings and for our recent results (1,2). The model was implemented by a set of ordinary differential equations and analyzed by simulation. We investigate the dynamics of the G1 to S transition by simulation in several genetic and nutritional set ups and in response to different signalling pathways. The model was found highly consistent with experimental data. The main control of the G1 to S transition is given by the requirement for a critical cell size (Ps) to enter S phase. The model has been shown to be able to correctly estimate Ps in various growth conditions. Sensitivity analysis of Ps indicate that it is an emergent property of the network, dependent also from growth rate. This fact supports a new interpretation on the reported role of ribosome biogenesis in controlling Ps. 1. L. Alberghina, R.L. Rossi, L. Querin, V. Wanke, and M. Vanoni “A cell sizer network involving Cln3 and Far1 controls entrance

into S phase in the mitotic cycle of budding yeast” – J. Cell Biol. 167, 433-443 (2004)2. R.L. Rossi, V. Zinzalla, A. Mastriani, M. Vanoni and L. Alberghina “Subcellular localization of the cyclin dependent kinase

inhibitor Sic1 is modulated by the carbon source in budding yeast” – Report - Cell Cycle 4, 1798-1807 (2005)

http://www.btbs.unimib.it/indexuk.htm (Keywords: Research-groups-containing: cell cycle)http://www.unimib.it

S1b-3 Circadian systems of cyanobacheria Takao Kondo Division of Biological Science, Graduate School of Science, Nagoya University and CREST/SORST, JST, Japan Contacts: kondo@bio.nagoya-u.ac.jp

Cyanobacteria are the simplest organisms that exhibit circadian rhythms. In the cyanobacterium, Synechococcus elongatus PCC 7942, three genes (kaiA, kaiB and kaiC) were identified to code essential components of the circadian clock. As we found robust circadian cycling of KaiC phosphorylation even without kaiBC mRNA accumulation, we attempted to reconstitute the oscillation of KaiC phosphorylation in vitro. By incubating KaiC with KaiA, KaiB and ATP, we found the self-sustainable circadian oscillation of KaiC phosphorylation. The in vitro oscillation of KaiC phosphorylation persisted for at least three cycles and the period was compensated against temperature change. Furthermore, changes in circadian period observed in vivo in various KaiC mutant strains were consistent with those measured in vitro when the incubations were carried out with the respective mutant KaiC proteins. These results demonstrate that the oscillation of KaiC phosphorylation is the primary pacemaker of the cyanobacterial circadian clock.We analyzed the in vitro KaiC phosphorylation cycle from four aspects as follows; 1) interaction of KaiA and KaiB to KaiC,

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2) interactions of two phosphorylation site, 3) energetics of the phosphorylation cycle of KaiC and 4) interactions among KaiC hexamers. From these analyses, we will propose a circadian programs of three proteins system for robust and tunable oscillations that tick biological time in the living cell.

http://www.bio.nagoya-u.ac.jp/seminar/b1.html (in Japanese)http://www.bio.nagoya-u.ac.jp/english/index.html (in English)

S1b-4 Analysis and synthesis of mammalian circadian clocks Hiroki R. Ueda Laboratory for Systems Biology, Center for Developmental Biology, RIKEN Contacts: uedah-tky@umin.ac.jp

The logic of complex and dynamic biological networks is difficult to elucidate without (1) comprehensive identification of network structure, (2) prediction and validation based on quantitative measurement and perturbation of network behavior, and (3) design and implementation of biological networks driven by the same logic as the original network. Mammalian circadian clock system is such a system consisting of complexly integrated regulatory loops and displaying the various dynamic behaviors including 1) endogenous oscillation with about 24-hour period, 2) entrainment to the external environmental changes (temperature and light cycle), 3) temperature compensation over the wide range of temperature, and 4) synchronization of multiple cellular clocks against the inevitable molecular noise. To elucidate complex structure and dynamic behavior of mammalian circadian clock, we comprehensively identify the transcriptional regulatory circuits composed of 20 transcription factors, and three type of DNA elements including “morning” element (Bmal1/Clock Binding element, E-box/E’-box), “day” element (DBP/E4BP4 binding element, D-box) and “night” element (RevErbA/ROR binding element, RREs). The following quantitative measurement and perturbation of clock circuits revealed that E-box/E'-box regulation represents a topological and functional vulnerability in mammalian circadian clocks, and also found the interesting property of peripheral circadian clocks. In this conference, we will also report a current progress in the synthesis of transcriptional circuits underlying mammalian clock and discuss the logic governing this complex and dynamic biological networks.References1. Ueda, H.R. et al. A transcription factor response element for gene expression during circadian night. Nature 418, 534-539 (2002).2. Ueda, H.R. et al. System-level identification of transcription circuit underlying mammalian circadian clocks. Nat. Genet. 37,

187-192 (2005).3. Sato T K, et al. Feedback repression is required for mammalian circadian clock function. Nat Genet. 38, 312-9 (2006).

http://www.cdb.riken.jp/jp/02_research/0202_creative20.html

S1b-5 Multi-loop architecture in clock circuits Andrew J. Millar University of Edinburgh

II S2b SYSTEMS BIOLOGY OF BASIC BIOLOGICAL SYSTEMS 10:30-12:30, October 10

Yeast Systems Biology Sub Hall 1S2b-1 Dynamic modeling of stress response of yeast cells Edda Klipp Max Planck Institute for Molecular Genetics, Berlin, Germany Contacts: klipp@molgen.mpg.de

Investigation of cellular systems is more and more supported by computational methods like bioinformatics and mathematical modeling, which is an important aspect of Systems Biology. A frequently used method is the description of reaction systems by sets of ordinary differential equations. The structure of the equations is established based on the knowledge about the network structure, i.e. about the relevant pathways and protein-protein interactions, while the parameters are determined from experimental observations, preferentially time course measurements.Using the power of such models, we investigate stress response processes in the yeast Saccharomyces cerevisiae. The adaptation of the cells to environmental changes like nutrient supply, pheromone stimulation or osmotic stress is mediated by signaling pathways that eventually regulate the expression of many genes. The products of such genes, in turn, regulate the metabolism or the cell cycle progression in order to compensate for or adapt to the external stimuli. The predictions of the models agree well with experimental results obtained under different stress conditions or using certain mutants. Simulations reveal properties of the signaling process and enlighten the roles of different components in the adaptation process. The cross talk between different networks and the regulation of cycle progression by signal transduction pathways will be discussed.The presented examples show that mathematical models are helpful to formulate experimental knowledge in a testable form, to explain hitherto unsolved phenomena, and to even predict the outcome of new experiments.

http://www.molgen.mpg.de/~ag_klipp

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S2b-2 Quantitative physiology of a cellular information sensing and relaying system Roger Brent The Molecular Sciences Institute, Berkeley, California, USA

I will review some of recent findings about the yeast pheromone response system from the Alpha project. Many of these findings are at least somewhat surprising. Some seem important, may be fundamental, in the sense that they may apply across eukaryotic biology for systems of this basic type.For signal dynamics (Yu et al., 2006), these include the fact that signal propagation is slow, taking minutes to reach the nucleus, that a each measurement point the signal shows a consistent pattern of rise, overshoot, correction, and decline toward a stable value, that overshoot correction depends on negative feedback, that the negative feedback(s) do not bring about densensitization (adaptation), and that we can experimentally decouple signal propagation time from signal amplitude. For equilibrium system output (in prep), findings include that this system does not undergo desensitization (adaptation) over longer times, that is not an amplifier, and that it is not a switch. Rather, the system goes to great lengths, across many steps, to transmit accurate information about extracellular signal concentration, as measured by the percent receptor occupied. Put another way, one of the functions of the system is to keep information in the signal, in this case information about measured pheromone concentration, from being degraded during the many stages of its transmission. This behavior is not a trivial consequence of the known reactions in the system but in one case we have established that proper behavior again involves a negative feedback. Using protein mass spectrometry, we have also undertaken a comprehensive search for feedbacks within the system. We have so far identified circa 100 candidate sites, and have shown that some are functional.The picture in 2006 is thus of progress gained from of patient multidisciplinary development and experimentation on a tightly defined model system in a model organism. By pursuing this course, and by maintaining a resolutely agnostic stance as to how the system might operate, we have discovered a number of basic attributes of this function. Our point of understanding seems roughly equivalent to the degree of understanding of nerve impulse transmission in the 1930s, with two major differences. First, simple concepts from information theory seem applicable to this system, and we are particularly excited that work to date has given us unexpected insight into the signal’s semantic content. Second, the pheromone response system operates within a genetically tractable organism for which genetic analysis is already yielding insight. This combination of disciplinary approaches to the study of a simple prototype system should continue to yield insights and may help define one thing that 21st century systems biology can be.http://www.molsci.org/

S2b-3 Interrogation of cellular networks Mike Tyers Samuel Lunenfeld Research Institute, University of Toronto, Toronto, Canada Contacts: tyers@mshri.on.ca

Systematic approaches to chart biological networks include global analyses of gene expression, deletion phenotypes, genetic interactions and protein interactions. We have used these approaches to investigate the long-standing problem of cell size homeostasis in budding yeast. Before commitment to division in late G1 phase, cells must achieve a minimum critical cell size, as dynamically regulated by nutrient conditions. To uncover new pathways that coordinate growth and division, we have determined the cell size phenome using population-level size selection and barcode microarray analysis. Hundreds of small (whiskey or whi) and large (lge) mutants have been recovered and are currently being assembled into networks by systematic size epistasis and proteomic analysis.A crucial property of biological networks is compensation in gene function (buffering), as often revealed by genetic interactions. Systematic interrogation of the genetic landscape will therefore require simultaneous and precisely controlled perturbation of multiple network nodes, a task most readily accomplished with small molecule probes. To this end, we have begun to assemble a collection of small molecules that exhibit genotype-specific toxicity, as scored against many dozens of deletion mutants that affect various aspects of cell biology. An initial chemical-genetic interaction matrix, a corresponding chemical-chemical interaction matrix and possible implications for drug discovery will be presented.

http://www.mshri.on.ca/tyers/

S2b-4 Sources and control of cell to cell variation in the response of yeast to mating pheromone Alejandro Colman-Lerner, Rich Yu, Andrew Gordon, Tina Chin, C. Gustavo Pesce and Roger Brent The Molecular Sciences Institute, Berkeley, California, USA

We studied the quantitative behavior of a prototypical eukaryotic signal transduction system, the pheromone response pathway in yeast. We used fluorescent proteins, in transcriptional reporters and in fusions to pathway components expressed from native chromosomal promoters, to measure signal trasmission through the pathway in single cells. In this talk, I will focus on how faithfully this system relays information. We studied 1) how precisely pheromone dose information is “seen” at different steps down signal propagation in population of cells and 2) on the sources and control of variability system output in single cells. We found that at most points we measured, system output maps precisely onto the proportion of receptors that are bound by pheromone and that this behavior requires the operation of negative feedbacks. We also found large cell to cell variation in system output. Only a small proportion of total cell-to-cell variation is caused by ‘gene expression noise’. Instead, variation is dominated by differences in the capacity of individual cells to transmit signals through the pathway (‘pathway capacity’) and to express genes into proteins (‘expression capacity’). Our results indicate that various aspects of system’s quantitative behavior, including the degree of cell to cell variation, are under genetic regulation. Taken together, our results highlight the importance of a quantitative and dynamic measurments for the understanding of information carrying systems.

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II S2c SYSTEMS BIOLOGY OF BASIC BIOLOGICAL SYSTEMS 14:00-16:30, October 10

Metabolomics and Bioprocess Sub Hall 1S2c-1 Bottom-up reconstruction of the human metabolic network based on Build-35 and bibliomic data B. Palsson, N. Hurlen, S. Becker, N. Jamshidi, M. Mo, I. Thiele Department of Bioengineering, UCSD, La Jolla, CA

A genome-scale metabolic network for H. sapiens has been constructed based on the annotated build-35 of the human genome sequence and a comprehensive evaluation of the published literature on human metabolism over the past 50 years. The reconstruction accounts for 1496 ORFs, and the metabolic network has 2766 metabolites and 3311 reactions. The network can be used to; 1) assess where our knowledge is weak or missing, 2) analyze HT data sets, and 3) perform in silico analysis of network properties. Examples of all three applications will be given.

http://gcrg.ucsd.edu/personnel/palsson.htm

S2c-2 Systems level analysis and engineering of industrial bacteria Sang Yup Lee Dept. Chemical and Biomolecular Eng., Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea Contacts: leesy@kaist.ac.kr

Recent advances in omics research and modeling and simulation tools are enabling systems-level understanding of cellular behaviors, and consequently systematic engineering of the organisms to achieve desired goals. We have been developing various mathematical and analytical tools. One of the important technologies we are employing for strain development is metabolic flux analysis, which allows quantitative analysis of all intracellular fluxes based on certain constraints cells must obey under the given conditions. Metabolic flux analyses have been carried out under various genetically and environmentally perturbed conditions using genome scale in silico models. In this talk, the approaches taken in my group using genome-scale metabolic flux analysis in developing various biotechnological processes. In particular, I will focus on metabolic pathway engineering of Escherichia coli and other microorganisms towards enhanced production of desired products. Combination of in silico analysis and actual metabolic engineering allowed efficient creation of strains having improved performance. Detailed procedure and results will be presented. Also, general strategies for the improvement of strain based on the systems level analysis, especially how to find gene deletion and amplification targets for strain engineering, will be presented. [This work was supported by the Korean Systems Biology Research Grant from the MOST.]

http://mbel.kaist.ac.kr

S2c-3 Metabolome analysis and synthetic biology Masaru Tomita Institute for Advanced Biosciences, Keio University, Human Metabolome Technologies, Inc. Contacts: mt@sfc.keio.ac.jp

We have developed a metabolome analysis method based on capillary electrophoresis time-of-flight mass spectrometry (CE/TOFMS). This technology has been applied to numerous fields such as medical diagnosis (blood, urine, tissue), food production (farm products, fermentation), environmental biology (soil microbes), and systems biology of model organisms (E.coli and other bacteria) at our institute. We have recently discovered a biomarker of acetaminophen-induced hepatotoxicity, ophthalmate being a sensitive biomarker of glutathione depletion (Soga 2006 J. Biol. Chem.).The metabolome technology has made “multi-omics” analysis possible. We systematically obtained multi-omics data sets for Escherichia coli BW25113 and its single gene deletion mutants. Our data covers the metabolome (CE-TOFMS), proteome (western blot, shotgun proteomics, and 2D-DIGE), fluxome (GC-MS and NMR) and transcriptome (real time RT-PCR and DNA microarray).Using the collected multi-omics data, a simulation model of central carbon metabolism was constructed and the dynamic responses of the model after pulse addition of glucose were compared with experimental results.Finally, I will describe our ongoing research on genome engineering with the ultimate goal of designing and synthesize useful microorganisms based on computer models.

http://www.iab.keio.ac.jp

S2c-4 A systems biology approach to identify and therapeutically exploit the weakness of the robust tumour metabolism

Marta Cascante1*, S. Marin1, G. Alcarraz1, P. Vizan1, A. Ramos1, S. Diaz1, P. de Atauri1, J.J. Centelles1, P. W-N. Lee2, V. Selivanov1

1Dept. Bioquímica i Biol. Molec., CeRQT-Parc Científic Barcelona (PCB), Associated Unit to CSIC, University of Barcelona, Barcelona,C./ Martí i Franqués 1, 08028 Barcelona, Spain, 2Harbor-UCLA Research and Education Institute, University of California, Los Angeles School of Medicine, USA.

Contacts: *Corresponding author E-mail: martacascante@ub.edu

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Metabolic profile is the end point of the signaling events, where changes caused by diseases may be reflected and so it could be of key importance in correlating genotype with altered cellular phenotypes.A package in C++ has been developed for the dynamic tracer-based Mass Spectrometry (MS) or NMR isotopomer data analysis, which is connected with underlying enzyme kinetics. A core module of isotopomer distribution could be linked with various tissue-specific kinetic models, constructed for glucose metabolic network. This tool is applied to analyze metabolic adaptations in cancer cells and hepatocytes based in both enzyme kinetic information and tracer-based metabolomic data. From this “in silico” model, simultaneous estimation of metabolic fluxes, involved in the different glycolytic/gluconeogenic hepatic futile cycles, have been performed under different glycolytic and gluconeogenic substrates present in the medium. This analysis showed the importance of metabolic flux redistribution through futile cycles in maintaining cellular homeostasis. These examples demonstrate advantages of our new method which is not restricted by steady state and makes use of the enzyme kinetic information.This work is a first step in the construction of “in silico” metabolic network flux simulators in different cell types that can be very useful to design new therapies in multifactorial chronic diseases as cancer or diabetes as well as to predict drug side effects.

http://www.bq.ub.es/bioqint/arecerca.html

II S3b SYSTEMS BIOLOGY OF BASIC BIOLOGICAL SYSTEMS 9:15-10:30, October 11

Developmental Systems Biology Sub Hall 1S3b-1 C. elegans early embryogenesis: global, local and evolutionary views Fabio Piano Center for Comparative Functional Genomics and Department of Biology, New York University Contacts: fp1@nyu.edu.

Once fertilized, animal embryos must follow a series of events that give rise to different cell identities raising important fundamental questions in development. We are using C. elegans early embryogenesis (EE) as a model for approaching metazoan development at a systems level. In recent years C. elegans has become a prime model for powerful high-throughput functional genomics approaches, including global RNAi-based analyses followed by time-lapse microscopy. These approaches are particularly useful for studying developmental processes since development can be regarded as driven by the complex dynamic interactions of thousands of genes and their products. Hence, functional genomics techniques that give insight into gene function on a global level have opened the door for decoding gene interaction networks that control development. Since many components of developmental networks are conserved in evolution, specific insights into the genome-wide architecture of developmental networks in C. elegans are likely to be important for understanding molecular networks driving developmental decisions in other metazoans, including humans. Yet key evolutionary network changes are likely to underpin evolution of development. Our approaches to tackle these problems will be discussed.

S3b-2 Interactions among the pigment cells of zebrafish give rise to turing pattern Shigeru Kondo Nagoya University, Japan Contacts: skondo@bio.nagoya-u.ac.jp

The question of how complex animal body patterns arise from seemingly disorganized or formless initial structures represents an intriguing challenge not only to biologists but also to mathematicians, physicists and chemists. In 1952, the British mathematician Alan Turing proposed a simple mathematical equation capable of generating a wide range of patterns commonly found in the natural world, such as stripes, spots and reticulations. This model, known as the reaction-diffusion model, mathematically demonstrates that the interaction between a local activator and a long-range inhibitor can give rise to various periodic structures in response to differences in their individual diffusion rates. Although it was clear to have the potential capability to solve the fundamental problem of embryology, the difficulty of proving in an experiment had obstructed the proof of this epoch-making theory for a long time.Animal skin patterns are ideal subjects to study the molecular basis of the Turing mechanism. They are visible from outside, and it is clear that they form without any prepattern because most skin patterns usually are not similar to the inside structures. We discovered in 1995 that the skin pattern of a certain tropical fish changed continuously so that a Turing model might predict, and it became proof that the principle of Turing was actually working in a living thing. By using zebrafish as a new experimental system, we are trying to clarify the molecular network that constructs the putative Turing system.This research is funded by Riken(CDB), Grant in Aid “Gakujutu-Sousei”, and “Genome” from MEXT.

http://www.bio.nagoya-u.ac.jp/~z3/index.html

S3b-3 Quantitative analysis of C. elegans embryogenesis Shuichi Onami RIKEN Genomic Sciences Center, Japan Contacts: sonami@gsc.riken.jp

An embryo is a temporally and spatially dynamic system made up of many components. Quantitative analysis is essential for understanding such a large-scale dynamic system, in which actual behavior of the systems under various conditions is measured, mathematical models of the systems are created based on the measured behavior, the created models are refined by comparing

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actual behavior of the systems and simulated behavior of the models, and then the refinement of the model is repeated. To find basic principles of animal development, I am studying C. elegans embryogenesis using quantitative analysis. In this talk, I will present our quantitative cell division pattern analysis of RNAi embryos. In this analysis, position of nuclei in RNAi embryos are four-dimensionally measured using an image processing-based automated system and functions of genes are predicted from statistical comparisons of cell division patterns of these embryos. I will then present our quantitative analysis on molecular mechanisms that determine arrangement of cells in the embryo. I will discuss how computer simulations and image-processing-based in vivo measurements revealed the mechanism for male pronuclear migration and that for the symmetric/asymmetric positioning of nucleus in one-cell embryos. Finally, I will present recent progress of our research.

http://www.so.bio.keio.ac.jp, http://www.gsc.riken.jp

II S3e SYSTEMS BIOLOGY OF BASIC BIOLOGICAL SYSTEMS 11:00-12:30, October 11

Systems Neurobiology Sub Hall 1S3e-1 Understanding molecular complexity at the neuronal synapse August B Smit and Ka Wan Li Dept. Molecular & Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam,

The Netherlands Contacts: guus.smit@falw.vu.nl

Synapses are the central elements of communication between brain cells. The unsurpassed capacity of the brain to store and retrieve information, to make associations and to adapt to a changing environment are all considered to arise primarily from molecular adjustments in synapses. Synaptic mal-adaptations are known to cause or contribute to disease. Many drugs currently prescribed for brain disorders have known synaptic targets, however, the indirect effects on the synaptic protein network are poorly understood. Understanding the effects of drugs, or perturbations in general, on the complete synaptic protein/gene network is highly relevant both for a better understanding of synapse function and the identification of candidate proteins for future drug development. Therefore, it is crucial to understand the functional organization of the synaptic proteins network. Based on novel quantitative proteomics data, we work towards the construction of computational models, which explain how a complex protein network drives synaptic functions, and which predict its adaptive capacities in response to environmental cues, such as behavioral challenges and pharmacological interventions. Specific objectives are to provide targets for synaptic modulation and to dissect disease phenotypes by identifying crucial nodes and connectivity of the network. http://www.cncr.nl/mcn/index.html

S3e-2 Modelling structure and function of the post-synaptic proteome J Douglas Armstrong1, Andrew J Pocklington1 & Seth GN Grant2

1School of Informatics, Institute for Adaptive and Neural Computation, University of Edinburgh, 2Wellcome Trust Sanger Institute, Cambridge

Contacts: douglas.armstrong@ed.ac.uk

Proteomic study of the mammalian synapse has generated an extensive list of molecular components, revealing it as one of the most complex biological systems. While fundamental to information processing, behaviour and cognitive disorders, the molecular architecture of signalling in the synapse and its relation to higher-level function is now beginning to emerge. We present a model of the synaptic proteome that captures its structural organisation. Each component is annotated with information describing its molecular features/domains, evolutionary orthologues across 19 species, measurements of gene/protein expression in brain regions and functional annotation from yeast, fly, mouse and human. The model reveals a highly integrated and modular structure. Modules, defined by molecular interactions, not only share common network properties but also functional annotation, regional expression patterns and evolutionary origins. The picture that emerges is of a set of input modules (e.g. receptor complexes) that are closely linked to higher order cognition (and disorders), of more recent evolutionary origin and with high regional variation in the brain. These then link through more central processing modules to a series of output modules (e.g. gene regulatory complexes) that are more closely related to vital functions, ancient evolutionary origin and little variability across the brain.

www.inf.ed.ac.uk/~jda

S3e-3 Systems analysis of spike-timing dependent synaptic plasticity Shinya Kuroda1, Hidetoshi Urakubo1, and Robert C. Froemke2

1CREST, Japan Science and Technology Agency, Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Japan, 2Department of Otolaryngology, University of California, San Francisco, USA

Contacts: skuroda@bi.is.s.u-tokyo.ac.jp

Spike timing-dependent synaptic plasticity (STDP), which depends on the relative timing of pre- and postsynaptic spiking, is thought to play an important role in neural development and information storage. However, mechanism of spike-timing detection in STDP

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remains unclear. To understand the mechanism of spike-timing detection in STDP, we developed a computational model of STDP, and found that long-term potentiation (LTP), but not long-term depression (LTD), could be reproduced, indicating an existence of an unknown mechanism for spike-timing detection in STDP. We searched a requirement for spike-timing detection in LTD, and predicted an allosteric kinetics of NMDARs. We experimentally validated the prediction of allosteric kinetics of NMDARs based on the NMDARs-mediated EPSPs. Furthermore, the allosteric kinetics of NMDARs was valid over more complex spike-timing dependent synaptic plasticity in experiments. Thus, our results indicate that a simple allosteric kinetics of NMDARs can code complex spike-timing information into synaptic plasticity. In this talk, I will discuss the possible role of the allosteric kinetics of NMDARs in coding of complex spike-timing information into STDP, which may restructure neural circuits and embed experiences into the brain.

http://www.kurodalab.org

II S3h SYSTEMS BIOLOGY OF BASIC BIOLOGICAL SYSTEMS 14:00-16:30, October 11

Signal Transduction Sub Hall 1S3h-1 Cell-signaling dynamics in time and space Boris N. Kholodenko Thomas Jefferson University

We employ computational and experimental approaches to reveal kinetic and molecular factors that control the temporal dynamics of the EGFR signaling network, including transient versus sustained activation patterns, discontinuous bistable dynamics and oscillations. Quantitative analysis of signal transduction is confronted by a combinatorial explosion in the number of feasible molecular species presenting different states of signaling networks that include receptors and scaffolds with multiple binding domains. We show that a mechanistic description of a highly combinatorial network may be drastically reduced using a “domain-oriented”, macro-modeling framework. Using this approach, we explored the role of the scaffold protein GAB1 in the control of mitogenic (Ras/MAPK) and survival (PI3K/Akt) signaling. The results demonstrate that the essential function of GAB1 is to enhance PI3K/Akt activation and extend the duration of Ras/MAPK signaling. The spatial separation of kinases and phosphatases in MAPK cascades may cause precipitous spatial gradients of phosphorylated kinases with high concentration near the cell surface and low in the perinuclear area. The results suggest that there are additional (besides diffusion) mechanisms that facilitate signaling to distant targets. They may involve endocytosis, scaffolding and active transport of signaling complexes by molecular motors. We show how traveling waves of phosphorylated kinases spread the signals over long distances. In addition to mechanistic modeling, an integrative, modular approach to inferring the structure of cellular signaling and gene networks is proposed. We demonstrate how dynamic connections leading to a particular module (e.g., an individual gene/protein or a cluster) can be retrieved from experimentally measured network responses to perturbations influencing other modules. References. Kholodenko, B.N. (2006) Cell-signalling dynamics in time and space. Nat Rev Mol Cell Biol, 7, 165-176.Sontag, E., Kiyatkin, A. and Kholodenko, B.N. (2004) Inferring dynamic architecture of cellular networks using time series of gene expression, protein and metabolite data. Bioinformatics, 20, 1877-1886.

http://www.cellnetworks.org

S3h-2 Emerging principles of living systems Hans V. Westerhoff 1,2, Frank Bruggeman1,2, Barbara Bakker2 and Jacky L. Snoep1,2,3

1Manchester Center for Integrative Systems Biology, The University of Manchester, UK, EU, 2BioCenter Amsterdam, Vrije Universiteit Amsterdam, NL, EU and 3Department of Biochemistry, University of Stellenbosch, South Africa

Contacts: hans.westerhoff@manchester.ac.uk

Much of the primary function of living cells is in chemical and physical processes, such as the generation of amino acids for protein synthesis or the contraction of actomyosin. These primary processes are carried out by metabolic and other pathways of substantial length, which are activated by signal transduction and gene-expression pathways. One issue is how the dynamics of any of these pathways and the flux through any of these processes is controlled by the various molecular processes. This control turns out to be a system property that cannot be assessed from the study of individual steps of the pathway alone.It is an important characteristic of living systems that the individual reaction rates in these pathways need to be regulated so as to stay in tune with each other whilst they change strongly with changing functional requirements. This regulation is effected through gene expression but also through metabolic regulation and is again a systems property rather than a property of the individual processes that are being regulated.This presentation will show that both control and regulation are indeed system properties and that both are subject to a number of general laws or principles. These laws relate to robustness (lack of control), fragility, homeostasis, adaptation ad differentiation. We shall discuss how recognition of some of these principles may help understand important aspects of multifactorial disease and lead to new strategies for drug design. http://www.mcisb.org/http://www.bio.vu.nl/hwconf/

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S3h-3 Ligand-dependent cell fate control of ErbB signaling network in breast cancer cells Mariko Hatakeyama Cellular Systems Biology Team, RIKEN Genomic Sciences Center Contacts: marikoh@gsc.riken.jp

Over-expression and mutation of ErbB receptors are implicated with various kinds of human cancers. On the other hand, ErbB receptor ligands, epidermal growth factor (EGF) and heregulin (HRG) induce transient and sustained extracellular signal-regulated kinase (ERK) and protein kinase B/Akt activities in human MCF-7 breast cancer cells, of which distinct kinetics result in cellular proliferation and differentiation, respectively. Comprehensive analysis of ErbB signaling network is necessary to understand the mechanism of cell fate control and cancer development. In our study, we quantitatively analyzed time-course events of the intracellular signaling and transcription that are initiated by the EGF and HRG. Our results indicated that ligand-induced intracellular signaling and early transcription was first regulated in ligand dose-dependent manner. However, those early transcripts crosstalk with intracellular signaling and then convert dose-dependent signals to binary response that may determine cell fate. We will discuss about mechanistic properties of ErbB receptors and its contribution for controlling cellular network based on the result given by mathematical modeling. 1. Naka, et al. Compensation effect of MAPK cascade on formation of Phospho-protein gradient. BioSystems 83, 2-3,

167-177, 2006.2. Suenaga, et al. Novel mechanism of interaction of p85 subunit of PI3K and ErbB3 receptor-derived phosphotyrosyl

peptides. J. Biol. Chem. 280, 1321-1326, 2005.3. Kimura, et al. Inference of S-system models of genetic networks using a cooperative coevolutionary algorithm.

Bioinformatics 21, 1154-1163, 2005.4. Hatakeyama, et al. Transformation potency of ErbB heterodimer signaling is determined by B-Raf kinase. Oncogene 23,

5023-5031, 2004.5. Suenaga, et al. Tyr317 phosphorylation increases Shc structural rigidity and reduces coupling of domain motions remote

from the phosphorylation site as revealed by molecular dynamics simulations. J. Biol. Chem. 279, 4657-4662, 2004.6. Hatakeyama, et al. A computational model on the modulation of MAPK and Akt pathways in heregulin induced ErbB

signaling. Biochem J., 373, 451-463, 2003. 7. Suenaga, et al. Molecular dynamics, fee Energy and SPR analyses of the interactions between SH2 domain of growth factor

receptor binding protein 2 and ErbB phosphotyrosyl peptides. Biochemistry (U.S), 42, 5195-5200, 2003. http://csb.gsc.riken.jp/

S3h-4 Rules for modeling signal-transduction systems William S. Hlavacek Center for Nonlinear Studies, Los Alamos National Laboratory, U.S.A. Contacts: wish@lanl.gov

The behavior of a signal-transduction system depends on the dynamics of protein interactions. The site-specific details of these interactions can be represented using formal rules, which can be visualized using graphs. A set of rules can be processed to automatically generate a dynamical model that accounts comprehensively for the protein complexes implied by the interactions encoded in the rules. The number of possible complexes is often large, which limits conventional approaches to model specification. After summarizing the motivation for rule-based modeling, I will introduce the method, including recent improvements that should facilitate high-throughput modeling and simulations of large-scale networks, and then illustrate how a rule-based approach is being used to model aspects of epidermal growth factor and antigen-recognition receptor signaling. Finally, I will point to future challenges and the promise of an extensible standardized modeling language suited for the complexities of cellular signaling.William S. Hlavacek, James R. Faeder, Michael L. Blinov, R. G. Posner, M. Hucka, W. Fontana (2006) Rules for modeling signal-transduction systems. Sci. STKE 2006, re6. http://www.t10.lanl.gov/wish/

S3h-5 Reaction cycles in the spatial and temporal organization of cell signaling Philippe Bastiaens EMBL Heidelberg, Germany

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III S2e FRONTS IN SYSTEMS BIOLOGY 10:30-12:30, October 10

Network Biology Sub Hall 2S2e-1 Interactome networks Marc Vidal Center for Cancer Systems Biology (CCSB), and Department of Cancer Biology, Dana-Farber Cancer Institute, Department of

Genetics, Harvard Medical School Contacts: marc_vidal@dfci.harvard.edu

For over half a century it has been conjectured that macromolecules form complex networks of functionally interacting components, and that the molecular mechanisms underlying most biological processes correspond to particular steady states adopted by such cellular networks. However, until recently, systems-level theoretical conjectures remained largely unappreciated, mainly because of lack of supporting experimental data.To generate the information necessary to eventually address how complex cellular networks relate to biology, we initiated, at the scale of the whole proteome, an integrated approach for modeling protein-protein interaction or “interactome” networks. Our main questions are: How are interactome networks organized at the scale of the whole cell? How can we uncover local and global features underlying this organization, and how are interactome networks modified in human disease, such as cancer? DFCI Center for Cancer Systems Biology (CCSB)http://ccsb.dfci.harvard.edu/home.htmlVidal Labhttp://vidal.dfci.harvard.edu/

S2e-2 Protein network comparative genomics Trey Ideker University of California San Diego Contacts: trey@bioeng.ucsd.edu

With the appearance of large networks of protein-protein and protein-DNA interactions as a new type of biological measurement, methods are needed for constructing cellular pathway models using interaction data as the central framework. The key idea is that, by comparing the molecular interaction network with other biological data sets, it will be possible to organize the network into modules representing the repertoire of distinct functional processes in the cell. Three distinct types of network comparisons will be discussed, including those to identify:(1) Protein interaction networks that are conserved across species(2) Networks in control of gene expression changes(3) Networks correlating with systematic phenotypes and synthetic lethalsUsing these computational modeling and query tools, we are constructing network models to explain the physiological response of yeast to DNA damaging agents.Relevant articles and links:Yeang, C.H., Mak, H.C., McCuine, S., Workman, C., Jaakkola, T., and Ideker, T. Validation and refinement of gene regulatory pathways on a network of physical interactions. Genome Biology 6(7): R62 (2005).Kelley, R. and Ideker, T. Systematic interpretation of genetic interactions using protein networks. Nature Biotechnology 23(5):561-566 (2005).Sharan, R., Suthram, S., Kelley, R. M., Kuhn, T., McCuine, S., Uetz, P., Sittler, T., Karp, R. M., and Ideker, T. Conserved patterns of protein interaction in multiple species. Proc Natl Acad Sci U S A. 8:102(6): 1974-79 (2005).Suthram, S., Sittler, T., and Ideker, T. The Plasmodium network diverges from those of other species. Nature 437: (November 3, 2005).

http://www.pathblast.orghttp://www.cytoscape.orgAcknowledgements: We gratefully acknowledge funding through NIH/NIGMS grant GM070743-01; NSF grant CCF-0425926; Unilever, PLC, and the Packard Foundation.

S2e-3 Genome network project in Japan Yoshihide Hayashizaki Genome Exploration Research Group, Riken Genomic Sciences Center, Riken Yokohama Institute, Japan Contacts: yosihide@gsc.riken.jp

Analysis of the Fantom-3/GenomeNetwork transcriptome dataset, including 158,807 cDNAs, 11.5 million CAGE tags and 2.4 million GSC tags, suggests that mammalian genomes express an unprecedented number of independent transcripts, of which about half are grouped in Transcriptional Unit (TU) containing non-coding RNAs, while a considerable fraction of these was shown to be non-coding RNA variant of TU containing protein coding mRNAs. In this very large transcript collection, we found extensive transcription overlap identifying a very large number of novel RNAs sense-antisense (S/AS) potential transcript pairs, to which a large number of transcribed repeats and repeat containing RNA has to be added. These S/AS show significant coexpression and are regulated in

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various tissues, organs and cells in our analysis. Experimental evidence shows that RNAs constituting S/AS pairs regulate each other concentration, through RNA-based gene regulation mechanisms such as RNAi intermediates.The FANTOM full-length cDNAs are the collection of the elements and the integrated database provides us the tool to understand the molecular system connecting gene to phenotype. Our next goal is focused on constructing the system to accelerate the analysis of the network of transcription. For this purpose, the deep CAGE technology, the technology to analyze physical binding of transcription factors and DNA, such as Chip on CHIP, and matrix RNAi were integrated into a pipeline of analysis. In this talk the future system to analyze genome network will be discussed.

http://www.gsc.riken.go.jp/eng/output/topics/genome.html

S2e-4 Single molecule imaging of motor proteins in living cells - deciphering physical networks of molecular motions

Hideo Higuchi and Tomonobu M Watanabe Biomedical Engineering Research Organization, Tohoku University, Japan

Motor proteins, e.g., myosin, kinesin and dynein, are involved in membrane transport in a cell. Single-molecule measurements in an in vitro assay provide us great deal of information of motor mechanism. However, physiological conditions in the cell are much different from those in vitro. Here, we developed novel techniques to observe the elementary steps of the movement of motor proteins in living cells. To record the movement of motor proteins in cells with high spatio-temporal resolution, membrane Receptor (HER2) was labeled with stable and intense Quantum dots via antiHER2. They were endocytosed into a breast cancer cell in which HER2 was overexpressed. We observed the movements of the transported vesicle of antiHER2-QD in three dimensions using a new microscopic system. AntiHER2-QD was transported along an actin filament by myosin VI, and toward the nucleus by dynein on microtubules. The position of movement was analyzed with 2 nm and 0.3 ms resolutions. The movement along the membrane consisted of 29 and 16 nm steps. The movements toward and away from the nucleus consisted of successive 8 nm steps. This movement will be generated by kinesin, also composed of sequential 8 nm steps. Thus, the techniques we developed were new and useful tools for investigation of molecular functions of proteins.

http://www.cir.tohoku.ac.jp/higuchi-p/NanoSystem/index.htmhttp://web.tubero.tohoku.ac.jp/~nim/

III S3c FRONTS IN SYSTEMS BIOLOGY 9:15-10:30, October 11

Complex Systems Biology Sub Hall 2S3c-1 Interaction balance coordination as organizing principle in complex systems biology Mihajlo Mesarovic, Sree N.Sreenath and Girish Balakrishnan Complex Systems Biology Center, EECS, Case Western Reserve University Contacts: mdm5@case.edu

Complexity and sophistication of behavior of eukaryotes depend directly on their genome regulatory functions. Evidence indicates that evolution of eukaryotes is accompanied with increase in genetic resources allocated to regulatory functions. In human more than 90% of the genetic materials are protein non-coding, including introns -considered as junk genes-but is identified as performing vital regulatory functions leaving only 1.5% for exon-active genes. Progress in understanding complexity in systems biology will depend on understanding eukaryote’s regulatory functions.Obstacles to progress are conceptual and representational. Conceptually engineering concepts like feedbacks - negative and positive - are dominant regulatory motifs in systems biology. They are insufficient to understand organized complexity of eukaryotes. Organizational sciences and in particular mathematical multilevel hierarchical systems theory provide a wealth of new motifs for understanding in systems biology. Two case studies will be presented:• Explanation of angiogenesis as an exemplification of Interaction Balance Coordination Principle (IBCP) not only in cancers growth but also in metastasis (non-local distant action) as well in neural growth. • Modular coordination in JAK-STAT in myeloproliferative diseases.Representationaly, the focus in systems biology should not be restricted to quantification. Non-numerical branches of mathematics are more appropriate since biological phenomena cannot be represented with the precision of classical physics. Result of, mathematical general systems theory will be presented proving an exceedingly broad applicability of IBCP.New direction in systems biology research is needed for a search for coordination motifs as well as experimental validation of IBCP and other newly discovered motifs.

http://eecs.case.edu/people/faculty/mdm5

S3c-2 Coordination of gene expression by RNA operons Jack D. Keene Molecular Genetics & Microbiology, Duke University Medical Center, Durham, N.C. USA

The organization of genes along the genomes of higher eukaryotes does not correlate well with the functions of their encoded proteins as these genomes do not contain DNA operons like bacteria. For example, eukaryotic genes that are clustered in “expression

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neighborhoods” may be co-expressed but they do not appear to be functionally related to one another. Studies have suggested that eukaryotic transcription is leaky, sometimes stochastic, and probably not as precisely coordinated as previously thought. However, since the question of how eukaryotic gene expression is coordinated is essentially unknown, it has been assumed that dispersed genes are coordinated by temporal activation of their promoters. The Posttranscriptional RNA Operon model offers a mechanism of coordinated expression for higher eukaryotes that is based on the organization of functionally-related eukaryotic mRNAs within messenger ribonucleoprotein complexes (mRNPs). RNA-binding proteins (RBPs) and microRNAs both interact with discrete groups (classes or modules) of mRNAs that can be regulated together to provide collective functional outcomes and coordinated gene expression networks. These RNA operons or regulons can coordinate and couple mRNA decay, mRNA translation, splicing, export or localization of functionally related genes. I will discuss combinatorial interactions of RBPs and microRNAs that regulate posttranscriptional RNA operons.

http://mgm.duke.edu/faculty/keene/index.htm

S3c-3 Applications of complex systems biology to the study of neural systems Kenneth A. Loparo EECS Department, Case Western Reserve University Contacts: kenneth.loparo@case.edu

In this talk we will discuss the role of “complexity” in the study of the dynamics of neural systems and how the analysis of complex physiological time series is related to health and disease. Of particular interest is the dynamical process of neural plasticity in developing organisms. In this context, the “triple helix” of nature-nurture-niche plays a critical role in the neurodevelopmental process. Developmental sleep physiology recognizes this interplay and can quantify this interaction through a computational description of the process of “ontogenetic adaptation”. Understanding how remodeling and restructuring of the neural circuits is affected by the interplay between genetics and environment can have a significant impact on a variety of diverse fields including genetics, behavior, developmental psychology, neurobiology, and medicine. Our approach is to develop a computational phenotype that can quantify the process of neurodevelopment and provide a deeper understanding of the role of sleep in the maturational process in developing organisms. Our computational work fills an important gap in integrative neurosciences by identifying biomarkers for neurodevelopment between the molecular and behavioral/cognitive level that can provide additional insight into the neurobiology and dynamical processes of maturation of brain networks in developing organisms. Using computational neurophysiological techniques, including dynamic analyses of temporal features and patterns that are associated with the sleep process, we are able to capture the dynamic interactions among multiple behaviors that comprise the sleep process. Applying these analyses of sleep as phenotypic markers of brain organization and maturation provides a more complete picture of how adaptation and remodeling relates to physiologic function and development.

http://www.case.edu

III S3f FRONTS IN SYSTEMS BIOLOGY 11:00-12:30, October 11

Control and System Theory for Systems Biology Sub Hall 2S3f-1 Robustness analysis of biological networks using sensitivity measures Francis J. Doyle III Dept. of Chemical Engineering, and Biomolecular Science & Engineering, University of California, Santa Barbara, USA Contacts: frank.doyle@icb.ucsb.edu

A property of particular interest in systems biology is the robustness of a biophysical network: the ability to maintain some target level of behavior or performance in the presence of uncertainty and/or perturbations. In biological systems, these disturbances can be environmental (heat, pH, etc.) or intrinsic to the organism (changes in kinetic parameters). While preliminary results are available for simple (low-dimensional, deterministic) biological systems, general tools for analyzing these tradeoffs are the subject of active research.In this talk we introduce tools from systems theory that elucidate design principles in these complex architectures through the analysis of robust and fragile regions of the network. The problems used to illustrate the issue are drawn from circadian rhythm gene networks, hence the tools are extended to deal with oscillatory systems. Examples are presented for Drosophila, Mouse, and Arabidopsis networks. Recent to address discrete stochastic models are also covered. Finally, we highlight some recent results that analyze robustness properties at the tissue level, where intercellular coupling appears to be responsible for the generation of robust rhythms.

http://doyle.chemengr.ucsb.edu

S3f-2 Feedback control regulation of cell division Pablo A. Iglesias The Johns Hopkins University Contacts: pi@jhu.edu

During cell division, cells must accurately duplicate and segregate their genetic material before rearranging their morphology so as to produce two daughter cells of equal size. To achieve this, mitosis proceeds as a well-ordered sequence of biochemical events

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involving the temporal and spatial distribution of a wide variety of proteins, regulated by with numerous checkpoints that rely on active feedback loops. In contrast, cytokinesis, the last step in the mechanical separation of the two daughter cells, is typically viewed as an open-loop process, despite the fact that aberrant cytokinesis can lead to tumorigenesis. In this talk we demonstrate that feedback loops are also employed during cytokinesis. Specifically, we will show the presence of mitotic-specific feedback pathways that regulate the location of actin motor and crosslinking proteins vital to cell division. This feedback loop is activated by mechanical perturbations that affect cellular shape. Our results will demonstrate how the study of cellular division can benefit from a systems-level approach.

http://www.ece.jhu.edu/~pi/

S3f-3 The architecture of cellular regulation John Doyle California Institute of Technology Contacts: doyle@caltech.edu

This talk focuses on architectural and organizational principles of cellular regulation, building on insights about the fundamental nature of complex biological and technological networks drawn from three converging research themes. 1) With molecular biology’s detailed description of components and growing attention to systems biology the organizational principles of biological networks are becoming increasingly apparent (www.sbml.org). 2) Advanced technology’s complexity is now approaching biology’s. While the components differ, there is striking convergence at the network level of architecture and the role of layering, protocols, and feedback control in structuring complex multiscale modularity. New theories of the Internet and related networking technologies have led to test and deployment of new protocols for high performance networking (www.hot.caltech.edu, netlab.caltech.edu). 3) A new mathematical framework for the study of complex networks suggests that this apparent network-level evolutionary convergence within/between biology/technology is not accidental, but follows necessarily from the universal system requirements to be efficient, adaptive, evolvable, and robust to perturbations in their environment and component parts. [1] H. El-Samad, H. Kurata , J.C. Doyle , C.A. Gross, and M. Khammash, 2005, Surviving Heat Shock: Control Strategies for

Robustness and Performance, PNAS 102(8): FEB 22, 2005[2] Jin C, Wei D, Low SH, Bunn J, Choe HD, Doyle JC,et al, FAST TCP: From theory to experiments IEEE NETWORK 19

(1): 4-11 JAN-FEB 2005[3] Doyle et al, (2005), The “Robust Yet Fragile” Nature of the Internet, PNAS 102 (41), October 11, 2005 [4] MA Moritz, ME Morais, LA Summerell, JM Carlson, J Doyle (2005) Wildfires, complexity, and highly optimized tolerance,

PNAS, 102 (50) December 13, 2005; ,[5] H El-Samad , A Papachristodoulou, S Prajna, J Doyle, and M Khammash (2006), Advanced Methods and Algorithms for

Biological Networks Analysis, PROCEEDINGS OF THE IEEE, 94 (4): 832-853 APR 2006[6] Kurata, H El-Samad, R Iwasaki, H Ohtake, JC Doyle, et al. (2006) Module-based analysis of robustness tradeoffs in the

heat shock response system. PLoS Comput Biol 2(7): July 2006[7] M Chiang, SH Low, AR Calderbank, JC. Doyle (2006) Layering As Optimization Decomposition, PROCEEDINGS OF

THE IEEE, to appear

http://www.cds.caltech.edu/sostools/http://www.cds.caltech.edu/~doyle/

III S3g FRONTS IN SYSTEMS BIOLOGY 14:00-16:30, October 11

Synthetic Biology Main HallS3g-1 Languages and grammars for programming in DNA Drew Endy MIT Biological Engineering, Massachusetts Institute of Technology Contacts: endy@mit.edu

Biology is going through a fundamental transition, from preexisting, natural, and evolving systems to synthetic, engineered, and disposable systems. Here, we’ll review how the adoption of past engineering lessons such as standardization and abstraction are beginning to make the process of engineering biology simpler, cheaper, and more reliable. We’ll also explore how and why engineers are beginning to redesign simple genomes from scratch. From these technical foundations we’ll discuss recent and imaginable future progress on the engineering of living organisms to process information, construct materials, produce chemicals, provide energy and food, and help maintain or enhance human health and our environment. The talk will end with a brief discussion for what needs to happen next.

http://mit.edu/endy/

S3g-2 Applications in systems and synthetic biology Adam Arkin University of California, Berkeley

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S3g-3 Impact of a whole genome cloning on systems biology Mitsuhiro Itaya Institute for Advanced Biosciences, Keio University Contacts: mita@ttck.keio.ac.jp

Most DNA cloning vectors cannot handle a large number of genes at one time. We have developed a method to transfer whole genomes from one bacterial species into another (1). The BGM cloning vector derived from the 4.2-Mb genome of Bacillus subtilis bacterium was suitable for target DNA, the 3.5-Mb genome of the nonpathogenic, unicellular photosynthetic bacterium Synechocystis. The resultant bacterium putatively named as CyanoBacillus, with a composite genome 7.7 Mb in size, grew only in the B. subtilis culture medium in which the cloning procedures were carried out. Technical breakthroughs unveiled for the first time biological significance such as exclusiveness of the second RNA operon genes (rrn), and structural requirement of symmetry on bacterial chromosome in vivo.(1) Itaya, M., Tsuge, K. Koizumi, M., and Fujita, K. Combining two genomes in one Cell: Stable cloning of the Synechosystis PCC6803 genome in the Bacillus subtilis 168 genome. Proc. Natl. Acad. Sci., U. S. A., 102, 15971-15976 (2005).

http://www.iab.keio.ac.jp/ja/jprofile_mitsuhiro_itaya.html

S3g-4 Adaptive response of a gene network to environmental changes by fittness-induced attractor selection Tetsuya Yomo Department of Bioinformatics Engineering, Graduate School of Information Science and Technology, Graduate School of

Frontier Biosciences and Complex Systems Biology Project, ERATO, JST, Osaka University Contacts: yomo@ist.osaka-u.ac.jp

Cells switch between various stable genetic programs (attractors) to accommodate environmental conditions. Signal transduction machineries efficiently convey environmental changes to gene expression. However, since the number of environmental conditions is larger than that of commensurate cellular programs, not every condition, notably those that are rarely encountered, have led to the evolution of a cognate signal transduction pathway. Here we show that in the absence of signal transduction, switching to the appropriate attractor state expressing the genes that afford adaptation to the external condition can occur. In a synthetic bistable gene switch in Escherichia coli in which mutually inhibitory operons govern the expression of two genes required in two alternative nutritional environments, cells reliably selected the “adaptive attractor” driven by gene expression noise. A mathematical model suggests that the non-adaptive attractor state is avoided because the lower cellular activity suppresses mRNA metabolism, leading to larger fluctuations in gene expression which renders the non-adaptive state less stable. Although attractor selection is not as efficient as signal transduction via a dedicated cascade, it is simple and robust and may represent the general primordial mechanism for adaptive responses that preceded the evolution of signaling cascades for the frequently encountered environmental changes.

http://www-symbio.ist.osaka-u.ac.jp/sbe.html

S3g-5 Programmable bacterial catalysts Vítor Martins dos Santos, Miguel Godinho de Almeida, Jacek Puchalka, Amit Khachane, Kenneth Timmis German Research Centre for Biotechnology (GBF), Division of Microbiology, Braunschweig, Germany Contacts: vds@gbf.de

We will report on the preliminary results of a transnational, recently begun project that aims at constructing a functioning, streamlined bacterial cell devoid of most of its genome and endowed with a series of highly coordinated, newly assembled genetic circuits for the biotransformation of a range of chloroaromatics into high added value compounds and that include circuits for synchronized behaviour, noise minimisation and/or low-temperature biocatalysis and, in addition, amenable to directed, accelerated evolution so that the function of each or some of the individual circuits can be optimised. This will be tested for the production of high added value compounds from chloroaromatics in bioreactors. By achieving such constructs as a proof-of-principle, it is aimed at establishing a solid, rational framework for the engineering of cells performing effectively and efficiently specific functions of biotechnological and medical interest. This encompasses the production of series of different, versatile circuits and the corresponding components that can be used as building blocks in circuit engineering. The proposed workflow intertwines mathematical modelling with wet-lab experimental work as an integral module at every stage.

www.helmholtz-hzi.de

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III S3i FRONTS IN SYSTEMS BIOLOGY 14:00-16:30, October 11

Novel computational environments for systems biology Sub Hall 2S3i-1 Linking text with knowledge - challenges in text mining for biology Junichi Tsujii Department of Computer Science, Faculty of Information Science and Technology, The University of Tokyo, The University of

Manchester and National Centre for Text Mining (NaCTeM), Manchester Interdisciplinary Biocentre Contacts: j.tsujii@manchester.ac.uk, tsujii@is.s.u-tokyo.ac.jp

While there are a few Text Mining tools on market, they hardly satisfy actual requirements of biologists. Simple application of data mining techniques to text does not work. Since language and text have their own inherent structures, it is essential for TM tools to be able to recognize and exploit their structures to reveal information encoded in them. However, the major difficulties in treating information encoded in language are caused by the nature of the mapping between surface linguistic forms and information conveyed by them. It is hugely ambiguous. Furthermore, the same information can be conveyed by using many different surface forms. Before more ambitious goals such as discovering new, hidden knowledge, we have to resolve these essential properties of the mapping between language and information.Although techniques have been developed in natural language processing (NLP) research to resolve the difficulties, they were considered, until very recently, non-deployable for large scale text mining. However, due to recent technological development in corpus-based NLP techniques, many of NLP techniques have become robust and efficient enough for large scale text mining applications. The progresses in the filed have been enormous, which will open up many possible applications of NLP-based Text Mining in the near future.

http://www-tsujii.is.s.u-tokyo.ac.jp/

S3i-2 Going with the flow: distributed computing for systems biology using Taverna Carole Goble The School of Computer Science, The University of Manchester, UK Contacts: carolegoble@manchester.ac.uk

Linking together the many hundreds of publicly available or privately generated data sets and analytical tools into discovery pipelines is a key necessity for Systems Biology, but also a costly and frustrating business. Workflows offer a flexible and systematic approach for representing and executing these in silico experimental protocols. The Taverna workbench, a product of the myGrid project (http://www.mygrid.org.uk), is an open source workflow system that enables the scientists themselves to design, build and run workflows that control the flow of data between web-enabled and local Java resources. It has been designed primarily for the Life Sciences, and developed with a great deal of support and practical feedback from bioinformaticians. Taverna is very popular. It is used for gene alerting, sequence annotation, proteomics, functional genomics, chemoinformatics, systems biology and protein structure prediction applications, amongst others. The background and philosophy behind Taverna will be presented, highlighting how it complements a data warehouse approach. A number of real examples of its use in Systems Biology will be presented. The need for further tools and better data publishing practices will be highlighted, as will reflections on the changes to scientific practice observed when biologists adopt a Taverna approach to scientific discovery.

http://www.cs.man.ac.uk/~carole

S3i-3 The DREAM project: establishing a community-based gold standard for systems biology Andrea Califano Columbia University Medical Center

S3i-4 The systems biology markup language (SBML): where it's been and where it's going Michael Hucka California Institute of Technology Contacts: mhucka@caltech.edu

A cornerstone of systems biology is the use of computational modeling, by which hypotheses can be cast into a quantitative form that can be tested systematically. The use of computational modeling by biologists promises to pave the way for more rigorous analyses of biological functions, and ultimately will lead to new and better treatments for disease.A crucial enabler for more widespread use of computational modeling in biology is reaching agreement on how to represent, store, and communicate models between software tools. The Systems Biology Markup Language (SBML) project is an effort to create a machine-readable format for representing computational models in biology. By supporting SBML as an input and output format, different software tools can operate on the same representation of a model, removing chances for errors in translation and assuring a common starting point for analyses and simulations. SBML has become the most successful effort in this direction so far, with over 100 software systems supporting it today.In this presentation, I will discuss the current state of SBML, including recent developments such as this year's finalization of Version

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2 of SBML Level 2. I will also survey some of the software tools that support SBML, and related projects that have arisen to support more effective use of computational models. Lastly, I will discuss expected future developments in SBML.

http://sbml.orghttp://bnmc.caltech.edu

S3i-5 MIRIAM and BioModels DB: curation and exchange of quantitative models Nicolas Le Novere EMBL-EBI, Hinxton, United Kingdom Contacts: lenov@ebi.ac.uk

With Computational Systems Biology now being "mainstream" life science, the generation and use of quantitative models is no longer a lonely exercise reserved to the unchallenged specialist. On the contrary, those models have to be verified and, if possible, reused. Beside the effort of developing common syntaxes, the community of modellers and tool developers recently focused on the semantics of models. MIRIAM is a standard that describes the conditions which a biological model should meet to be correctly understood and reused. The guidelines address the problem of the correspondance of the model with its reference description, the details of the creation process and the annotation of all model components. An effective way of increasing the exchange of models compliant with MIRIAM is to store them in a relational database. BioModels Database is a resource that stores curated versions of peer-reviewed models. After careful verification of the syntax and semantics of a model, including its simulation, a thorough annotation procedure ensures that the model will be retrieved quickly and its components easily identified. Models can be retrieved in various formats. It is expected that those efforts will increase the average quality of published quantitative models, and make those models a standard piece of each biologist's toolbox.

http://www.ebi.ac.uk/~lenov/

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BC21

W

hat m

akes

bio

logi

cal o

scil

lato

rs n

oisy

?Te

tsuy

a K

obay

ashi

, Shi

geki

Tsu

ji, K

azuy

uki A

ihar

a

BC22

S

yste

m-l

evel

per

turb

atio

n an

alys

is o

f m

amm

alia

n ci

rcad

ian

cloc

kTe

tsuy

a J.

Kob

ayas

hi, H

idek

i Uka

i, R

ikuh

iro

G. Y

amad

a, M

aki U

kai-

Tade

num

a, T

akao

K

ondo

, Hir

oki R

. Ued

a

BC23

P

redi

ctin

g re

gula

tion

of

the

phos

phor

ylat

ion

cycl

e of

Kai

C c

lock

pro

tein

usi

ng

mat

hem

atic

al m

odel

sH

isak

o Ta

kiga

wa-

Imam

ura,

Ats

ushi

Moc

hizu

ki

BC24

Fo

rwar

d an

d in

vers

e bi

furc

atio

n an

alys

is o

f a

synt

heti

c ge

ne r

egul

ator

y ne

twor

k

(the

rep

ress

ilat

or)

Stef

an M

uell

er, J

ames

Lu

BC25

M

odel

ing

the

G1/

S p

hase

tran

siti

on d

urin

g liv

er r

egen

erat

ion

A. B

eed,

S. L

egew

ie, P

. Wes

tern

ark,

H. H

erze

l

BC26

T

he e

ffec

t of

tran

scri

ptio

nal d

elay

s in

cyc

lic

bioc

hem

ical

Ger

man

A. E

ncis

o

BC27

G

enom

e-w

ide

iden

tifi

cati

on o

f m

orni

ng e

lem

ent r

egul

ator

s by

hig

h-th

roug

hput

cel

l-ba

sed

scre

enin

gH

iros

hi F

ujis

him

a, T

akey

a K

asuk

awa,

Hid

eki U

kai,

Ryo

taku

Kit

o, H

irok

i R. U

eda

BC28

S

yste

m-l

evel

iden

tifi

cati

on o

f ro

bust

and

sen

sitiv

e ge

ne e

xpre

ssio

nTa

keya

Kas

ukaw

a, T

etsu

ya J

. Kob

ayas

hi, R

ikuh

iro

G. Y

amad

a, J

ohn

B. H

ogen

esch

, H

irok

i R. U

eda

35

BC29

C

ell-

base

d sc

reen

ing

for

stab

ilit

y re

gula

tors

of

mam

mal

ian

cloc

k pr

otei

nsR

yota

ku K

ito,

Hir

oshi

Fuj

ishi

ma,

Hid

eki U

kai,

Yoic

hi M

inam

i, H

irok

i R. U

eda

BC30

K

inet

ic m

odel

ing

of g

ene

expr

essi

on. S

tudy

of

ace

oper

on g

enet

ic r

egul

atio

n in

E

sche

rich

ia c

oli c

ells

Kir

ill P

esko

v, O

leg

Dem

in

Yea

st S

yste

ms

Bio

logy

BY01

D

etec

ting

cel

l cyc

le r

egul

ated

gen

es o

f S.

pom

be b

y us

ing

nMD

S w

itho

ut s

inus

oida

l fi

ttin

gY-

H. T

aguc

hi

BY02

In

tegr

ativ

e st

rate

gy f

or c

onst

ruct

ing

a la

rge-

scal

e ce

ll c

ycle

mod

el in

sil

ico

Yuya

Fuk

ano,

Shu

nsuk

e Ya

mam

ichi

, Hir

oyuk

i Kur

ata

BY03

In

ferr

ing

phys

ical

mod

els

of p

rote

in-D

NA

bin

ding

fro

m h

igh-

thro

ughp

ut d

ata

Just

in B

. Kin

ney,

Gas

per

Tka

cik,

Cur

tis

G. C

alla

n, J

r.

BY04

P

rote

in-p

rote

in in

flue

nce

netw

orks

in S

acch

arom

yces

cer

evis

iae

Kar

thik

Ram

an, N

agas

uma

Cha

ndra

BY05

E

ngin

eeri

ng r

edox

bal

ance

in S

acch

arom

yces

cer

evis

iae

to r

educ

e ov

erfl

ow m

etab

olis

mG

outh

am V

emur

i, J

ens

Nie

lsen

, Lis

beth

Ols

son

BY06

D

iffe

rent

ial e

volu

tiona

ry c

onse

rvat

ion

of m

otif

mod

es in

the

yeas

t pro

tein

inte

ract

ion

netw

ork

Wen

-Shy

ong

Tzou

, Wei

-Po

Lee

BY07

A

naly

sis

of r

egul

ator

y ne

twor

ks o

f th

e m

itot

ic e

xit s

yste

m in

Sac

char

omyc

es c

erev

isia

eW

ee K

heng

Yio

, Utt

am S

uran

a, B

alta

zar

Agu

da

BY08

Q

uant

ifica

tion

of

uppe

r li

mit

Cdc

pro

tein

s do

sage

in S

. cer

evis

iae.

Yuki

Shi

miz

u-Yo

shid

a, H

isao

Mor

iya,

Hir

oaki

Kit

ano

BY09

O

rgan

izat

ion

of th

e ye

ast m

etap

hase

spi

ndle

Eug

enio

Mar

co, J

onas

F. D

orn,

Khu

loud

Jaq

aman

, Gre

gory

S. J

elso

n, G

aude

nz

Dan

user

, Pet

er K

. Sor

ger

BY11

D

ynam

ics

and

regu

lati

on o

f th

e he

tero

trim

eric

G-p

rote

in c

ycle

Tau-

Mu

Yi,

Hir

omas

a Ta

naka

, Tra

vis

Moo

re

BY12

In

vest

igat

ion

of f

erm

enta

tion

cha

ract

eris

tics

of

the

drug

res

ista

nce

gene

QD

R3

in S

. ce

revi

siae

Duy

gu D

ikic

iogl

u, P

inar

Pir

, Z. I

lsen

Ons

an, K

utlu

O. U

lgen

, Bet

ul K

irda

r,

Stev

e G

. Oli

ver

BY13

Y

east

sys

tem

s bi

olog

y ne

twor

kR

ober

ta M

usta

cchi

, Jen

s N

iels

en

BY14

C

ompu

tati

onal

ana

lysi

s of

rel

evan

t asp

ects

of

the

G1

to S

tran

siti

on m

odel

in b

uddi

ng

yeas

tM

atte

o B

arbe

ris,

Edd

a K

lipp

, Mar

co V

anon

i, L

ilia

Alb

ergh

ina

BY15

A

sys

tem

s bi

olog

y st

udy

of th

e ki

neti

cs o

f Sa

ccha

rom

yces

cer

evis

iae

resp

onse

to

oxid

ativ

e st

ress

indu

ced

by c

umen

e hy

drop

erox

ide

Lee

pika

Tul

i, A

na M

arti

ns, W

ei S

ha, P

edro

Men

des,

Vla

dim

ir S

hula

ev

Met

abol

omic

s an

d B

iopr

oces

s

BM01

In

sil

ico

anal

ysis

of

syst

emat

ic r

espo

nse

to th

e ch

ange

of

enzy

me

conc

entr

atio

n ba

sed

on

glyc

olys

is b

ioch

emic

al n

etw

ork

of S

acch

arom

yces

cer

evis

iae

Xue

lian

Yan

g, M

ing

Yan,

Lin

Xu,

Dec

hong

Kon

g, C

hang

qing

Liu

, Pin

gkai

Ouy

ang

BM02

S

imul

atio

n an

d an

alys

is o

f et

hano

l con

cent

rati

on r

espo

nse

to e

nzym

e am

ount

cha

nges

in

S. c

erev

isia

e gl

ycol

ysis

pat

hway

mod

elD

echo

ng K

ong,

Xue

lian

Yan

g, M

ing

Yan,

Cha

ngqi

ng L

iu, L

in X

u

BM03

C

onta

ct-d

epen

dent

indu

ctio

n of

per

sist

ence

Mic

hael

S. K

oeri

s, M

icha

el A

. Koh

ansk

i, K

yle

R. A

llis

on, G

abor

Bal

azsi

, Bor

is H

ayet

e,

Jam

es J

. Col

lins

BM04

S

yste

m a

naly

sis

and

expe

rim

enta

l val

idat

ion

of g

luco

se u

ptak

e ra

te b

y ph

osph

otra

nsfe

rase

sy

stem

in E

sche

rich

ia c

oli

Yous

uke

Nis

hio,

Yos

hihi

ro U

suda

, Kaz

uhik

o M

atsu

i, H

iroy

uki K

urat

a

BM05

C

alci

um-d

epen

dent

act

ivat

ion

and

mem

bran

e as

soci

atio

n of

the

nont

radi

tion

al m

aize

li

poxy

gena

se in

tran

sgen

ic r

ice

plan

tsO

ksoo

Han

, Kyo

ung

won

Cho

, Sun

gkuk

Jan

g

BM06

E

ffica

cy e

valu

atio

n of

gin

seno

side

Rb1

in b

rain

tiss

ue o

f m

ice

expo

sed

to im

mob

iliz

atio

n st

ress

usi

ng G

C/M

S b

ased

on

met

abol

omic

sB

ong

Chu

l Chu

ng, S

ang

Hee

Lee

, Sun

Yeo

u K

im, E

unjo

o H

Lee

BM08

A

naly

sis

of p

hyto

alex

ins

by h

igh

perf

orm

ance

liqu

id c

hrom

atog

raph

y-m

ass

spec

trom

etry

(H

PL

C-M

S)

foll

owin

g in

duct

ion

in D

atur

a m

etel

Els

adig

A. E

ltay

eb, F

atm

a A

l Bar

wan

i, B

asm

a A

l Sal

hi, T

. Kha

n

BM09

H

ypox

ic r

espo

nse

of h

uman

red

blo

od c

ell m

etab

olis

m a

sses

sed

by m

etab

olom

ics

and

sim

ulat

ion

Aya

ko K

inos

hita

, Mak

oto

Suem

atsu

, Yoi

chi N

akay

ama,

Tom

oyos

hi S

oga,

M

asar

u To

mit

a

BM10

M

etab

olom

e pr

ofili

ng o

f E

. col

i by

capi

llar

y el

ectr

opho

resi

s us

ing

nove

l tec

hniq

ues

of

mul

ti-w

avel

engt

h sp

ectr

al a

naly

sis

and

data

min

ing

Ars

en B

atag

ov, F

rank

Bag

anz

BM11

M

odel

ling

suc

rose

acc

umul

atio

n in

mat

urin

g su

garc

ane

Laf

ras

Uys

, Joh

ann

M. R

ohw

er

BM12

In

sili

co a

naly

sis

of th

e ca

uses

of

hete

roge

neou

s ge

ne e

xpre

ssio

ns in

live

r am

mon

ia

met

abol

ism

Yasu

hiro

Nai

to, H

iros

hi O

no, H

irom

u N

akaj

ima,

Mas

aru

Tom

ita

36

BM13

D

ynam

ic m

odel

ing

of E

sche

rich

ia c

oli c

entr

al c

arbo

n m

etab

olis

m b

ased

on

mul

ti-o

mic

s da

taN

obuy

oshi

Ish

ii, T

omoy

a B

aba,

Tom

oyos

hi S

oga,

Aki

o K

anai

, Ken

ji N

akah

igas

hi,

Mar

tin

Rob

ert,

Taka

shi T

ogas

hi, T

akas

hi H

iras

awa,

Mik

i Nab

a, K

enta

Hir

ai,

Am

inul

Hoq

ue, Y

uji K

akaz

u, K

aori

Sug

awar

a, S

aori

Iga

rash

i, Sa

tosh

i Har

ada,

Tak

eshi

M

asud

a, N

aoyu

ki S

ugiy

ama,

Kat

suyu

ki Y

ugi,

Kaz

uhar

u A

raka

wa,

Nay

uta

Iwat

a,

Yosh

ihir

o To

ya, T

suyo

shi I

was

aki,

Yoic

hi N

akay

ama,

Aki

ko H

agiy

a, M

asat

aka

Yosh

ino,

Ta

kaak

i Nis

hiok

a, K

azuy

uki S

him

izu,

Hir

otad

a M

ori,

Mas

aru

Tom

ita

BM14

A

com

puta

tion

al m

odel

of

card

iac

mit

ocho

ndri

a: s

imul

atio

n st

udie

s of

Ca2

+-d

epen

dent

re

gula

tion

and

sub

stra

te d

epen

denc

y of

mit

ocho

ndri

al e

nerg

y m

etab

olis

mR

yuta

Sai

to, N

obua

ki S

arai

, Sat

oshi

Mat

suok

a, A

kino

ri N

oma

BM15

M

etab

olic

net

wor

ks: c

onne

ctiv

ity

mat

rix-

base

d is

otop

omer

ana

lysi

s on

Mat

lab/

Oct

ave

Jun

Oht

a

BM16

In

sil

ico

geno

me

scal

e m

odel

ing

of P

seud

omon

as p

utid

a K

T24

40Se

ung

Bum

Soh

n, T

ae Y

ong

Kim

, San

g Yu

p L

ee

BM17

C

utD

B −

a d

atab

ase

of p

rote

olyt

ic e

vent

sYo

shin

obu

Igar

ashi

, Ale

xey

Ero

shki

n, S

vetl

ana

Gra

mat

ikov

a, K

osi G

ram

atik

off,

Jeff

rey

W. S

mit

h, A

dam

God

zik,

And

rei O

ster

man

BM18

M

etaA

naly

zer:

a s

oftw

are

tool

for

ana

lyzi

ng G

C-M

S d

ata

Inho

Par

k, K

iYou

ng L

ee, K

iryo

ng H

a, D

oheo

n L

ee, K

wan

g H

. Lee

BM19

P

redi

ctio

n of

sul

fur

stre

ss r

espo

nses

in A

rabi

dops

is th

alia

naR

yoko

Mor

ioka

, Shi

gehi

ko K

anay

a, M

itsu

ru Y

ano,

Mas

ami Y

. Hir

ai, K

azuk

i Sai

to

BM20

H

igh-

thro

ughp

ut p

rote

omic

iden

tifica

tion

of th

erm

al s

tabl

e pr

otei

ns f

rom

ther

mop

hilic

ba

cter

iaSh

ir-L

y H

uang

, Zha

ng-y

an H

uang

, Yu-

Jing

Zhu

ang,

Yu-

Lin

g Su

BM21

S

erum

met

abol

omic

pro

fili

ng to

stu

dy h

orm

one

acti

ons:

the

case

of

horm

onal

reg

ulat

ion

of g

ende

r di

ffer

ence

sL

ouis

a C

heun

g, H

ans

Sten

lund

, Pet

ra T

olle

t-E

gnel

l, T

hom

as M

orit

z,

Am

ilca

r F

lore

s-M

oral

es

Dev

elop

men

tal S

yste

ms

Bio

logy

BD01

G

row

th-b

ased

mor

phog

enes

is o

f ve

rteb

rate

lim

b bu

dYo

shih

iro

Mor

ishi

ta, Y

oh I

was

a

BD02

Pa

tter

n fo

rmat

ion

of p

lant

leaf

ven

atio

nH

iron

ori F

ujit

a, A

tsus

hi M

ochi

zuki

BD03

M

athe

mat

ical

mod

elin

g fo

r pa

tter

n fo

rmat

ion

of d

endr

ite

Kao

ru S

ugim

ura,

Tad

ashi

Uem

ura,

Ats

ushi

Moc

hizu

ki

BD04

T

he m

echa

nism

of

cell

dif

fere

ntat

ion

in B

acil

lus

subt

ilis

Dag

mar

Ibe

r, J

oann

a C

lark

son,

Mic

hael

D. Y

udki

n, I

ain

D. C

ampb

ell

BD05

M

odel

ing

and

sim

ulat

ion

of c

ardi

omyo

cyte

dev

elop

men

tH

itom

i Ito

h, Y

asuh

iro

Nai

to, M

asar

u To

mit

a

BD06

Id

enti

fica

tion

of

a ge

neti

c m

odifi

er o

f co

ngen

ital

hea

rt d

efec

t in

Type

IIA

pro

coll

agen

de

fici

ent m

utan

t mic

e su

gges

ts a

dyn

amic

reg

ulat

ory

syst

em in

car

diac

dev

elop

men

tP

aul L

. F. T

ang,

Ala

n Y.

B. T

ang,

Kat

hryn

S. E

. Che

ah, Y

ou-q

iang

Son

g

BD07

G

enom

e ba

sed-

met

abol

ic n

etw

ork

of M

annh

eim

ia s

ucci

nici

prod

ucen

s us

ing

upda

ted

geno

me

anno

tati

onTa

e Yo

ng K

im, J

in S

ik K

im, H

yun

Uk

Kim

, Jon

g M

yeon

g Pa

rk, H

yoha

k So

ng,

Sang

Yup

Lee

BD08

L

ogic

al m

odel

of

the

regu

lato

ry n

etw

ork

defi

ning

the

dors

al-v

entr

al b

ound

ary

of

th

e dr

osop

hila

win

g im

agin

al d

isc

Ait

or G

onza

lez,

Cla

udin

e C

haou

iya,

Den

is T

hief

fry

BD09

M

odel

ing

embr

yoni

c de

velo

pmen

t in

Dro

soph

ila

by e

volu

tion

ary

lear

ning

of

dyna

mic

al

syst

emSo

o-Ji

n K

im, J

e-K

eun

Rhe

e, J

in-W

u N

am, J

e-G

un J

oung

, Byo

ung-

Tak

Zha

ng

BD10

A

rtifi

cial

ant

s de

posi

t phe

rom

one

to s

earc

h fo

r re

gula

tory

DN

A e

lem

ents

Yunl

ong

Liu

, Hir

oki Y

okot

a

BD11

S

impl

ified

mod

els

of g

row

th f

or c

ells

and

tiss

ues

Eri

c M

jols

ness

, Ser

gey

Nik

olae

v, P

rzem

ek P

rusi

nkie

wic

z, A

lex

Sado

vsky

, S. F

adee

v,

Nik

olay

Kol

chan

ov

BD12

Fa

ctor

s di

ffer

enti

atin

g ce

ll f

ates

in a

pro

neur

al c

lust

erC

hao-

Pin

g (C

herr

i) H

su

BD13

A

mod

el f

or d

ynam

ic p

osit

ioni

ng o

f ce

ntro

som

es in

C. e

lega

ns e

mbr

yo b

ased

on

imag

e pr

oces

sing

ana

lyse

sA

kats

uki K

imur

a, S

huic

hi O

nam

i

BD14

S

imul

atin

g ev

olut

ion

and

deve

lopm

ent i

n an

imal

bod

y pl

anK

oich

i Fuj

imot

o, S

huji

Ish

ihar

a, K

unih

iko

Kan

eko

BD15

P

redi

ctio

n of

cel

lula

r be

havi

or d

urin

g ce

ll-s

orti

ng a

nd la

yer

form

atio

n of

cer

ebra

l cor

tex

by a

n in

sil

ico

cell

mod

elTa

kuya

Mae

da, I

tsuk

i Aji

oka,

Kaz

unor

i Nak

ajim

a

BD16

3D

Mon

te C

arlo

sto

chas

tic

sim

ulat

ion

of b

acte

rial

div

isio

n si

te p

lace

men

t on

a gr

aphi

cs

proc

essi

ng u

nit i

s si

gnifi

cant

ly f

aste

r th

an c

onve

ntio

nal C

PU

impl

emen

tati

onSa

tya

Nan

da V

el A

rjun

an, A

nton

Kra

tz, M

asar

u To

mit

a

BD18

G

ener

atio

n of

rob

ust l

eft-

righ

t asy

mm

etry

in th

e m

ouse

em

bryo

req

uire

s a

self

-en

hanc

emen

t and

late

ral-

inhi

biti

on s

yste

mTe

tsuy

a N

akam

ura,

Nao

ki M

ine,

Ets

ushi

Nak

aguc

hi, A

tsus

hi M

ochi

zuki

, M

asam

ichi

Yam

amot

o, K

enta

Yas

hiro

, Chi

kara

Men

o, H

iros

hi H

amad

a

BD19

A

n au

xin

tran

spor

t mod

el f

or r

egul

atio

n of

pla

nt o

rgan

init

iati

onH

enri

k Jo

nsso

n, M

arcu

s H

eisl

er, B

ruce

E. S

hapi

ro, E

llio

t M. M

eyer

owit

z, E

ric

Mjo

lsne

ss

BD20

D

egra

dati

on o

f co

ir p

ith

by th

e cy

anob

acte

rium

Osc

illa

tori

a sp

. and

its

valu

e ad

ded

prod

ucts

Seth

uram

an P

rabh

a, B

alai

ah A

nand

hraj

, Vis

wad

evan

Vis

waj

ith,

Pal

aniv

el V

aral

aksh

mih

, P

icha

imut

hu A

brah

am C

hris

toph

er, P

erum

al M

alli

ga

37

BD21

U

se o

f eu

geno

l as

seed

-bor

ne f

ungi

con

trol

ler

in p

akch

oi(b

rass

ica

chin

ensi

s L

.) f

or s

eed

coat

ing

tech

nolo

gyN

uchn

apa

Kot

abin

, Non

glak

Sai

thep

, Ara

ya J

atis

atie

nr, C

haiw

at J

atis

atie

nr

BD22

Q

uant

itat

ive

phen

otyp

ic a

naly

sis

of C

. ele

gans

em

bryo

sK

oji K

yoda

, Shu

ichi

Ona

mi

Syst

ems

Neu

robi

olog

y

BN01

S

yste

mic

mod

el f

or th

e C

a2+

sig

nall

ing

in th

e ne

uron

al c

ell

Cri

stin

a -

Mar

ia D

abu

BN02

Id

enti

fyin

g m

olec

ular

pat

hway

s un

derl

ying

syn

apti

c fu

ncti

on a

nd d

isea

seA

ndre

w J

. Poc

klin

gton

, Set

h G

. N. G

rant

, J. D

ougl

as A

rmst

rong

BN03

S

imul

atio

n of

che

mot

acti

c ne

twor

ks in

nem

atod

e C

. ele

gans

: is

ther

e an

y ch

ange

on

netw

orks

by

expo

sure

to io

nizi

ng r

adia

tion

?M

ichi

yo S

uzuk

i, T

etsu

ya S

akas

hita

, Tos

hio

Tsuj

i, K

ana

Fuk

amot

o, N

obuy

uki H

amad

a,

Yasu

hiko

Kob

ayas

hi

BN04

P

redi

ctio

n an

d va

lida

tion

of

a ti

min

g-de

tect

ion

mec

hani

sm f

or s

pike

tim

ing-

depe

nden

t pl

asti

city

Hid

etos

hi U

raku

bo, R

ober

t C. F

roem

ke, S

hiny

a K

urod

a

BN05

R

eali

stic

mod

els

of th

e N

MD

A r

ecep

tor

com

plex

Mel

anie

Ste

fan,

Nic

olas

Le

Nov

ere

BN06

A

kin

etic

mod

el o

f co

rtic

o-st

riat

al s

ynap

tic

plas

tici

tyTa

kash

i Nak

ano,

Tom

okaz

u D

oi, J

unic

hiro

Yos

him

oto,

Ken

ji D

oya

BN07

T

he h

eter

ogen

eity

of

astr

ocyt

ic c

alci

um r

espo

nses

may

be

regu

late

d by

con

cent

rati

on o

f in

trac

ellu

lar

enzy

mes

Isao

Got

o, K

iyoh

isa

Nat

sum

e

BN08

D

AR

PP

-32,

a c

ompl

ex in

tegr

ator

of

dopa

min

e an

d gl

utam

ate

sign

alli

ngE

ric

Fer

nand

ez, R

enau

d Sc

hiap

pa, J

ean-

Ant

oine

Gir

ault

, Nic

olas

Le

Nov

ere

Sign

al T

rans

duct

ion

BS01

H

ypot

hesi

s te

stin

g an

d m

odel

dis

crim

inat

ion

in y

east

osm

osen

sing

Joer

g Sc

habe

r, B

odil

Nor

dlan

der,

Dag

mar

a M

edra

la, S

tefa

n H

ohm

ann,

Edd

a K

lipp

BS03

Fi

ne tu

ning

of

Mdm

2-M

dmX

-p53

reg

ulat

ory

netw

ork

dyna

mic

s by

a r

eser

voir

com

plex

Sohy

oung

Kim

, Mir

it I

. Ala

djem

, Geo

ffery

B. M

cFad

den,

Kur

t W. K

ohn

BS04

A

naly

sis

of C

heA

-Che

Yp

affi

nity

and

ada

ptat

ion

erro

r in

bac

teri

al c

hem

otax

isYu

ri M

atsu

zaki

, Shi

nich

i Kik

uchi

, Mas

aru

Tom

ita

BS05

D

ynam

ic m

odel

ing

of th

e gp

130-

JAK

1-S

TAT

3 si

gnal

ing

path

way

in p

rim

ary

hepa

tocy

tes

Seba

stia

n B

ohl,

Tho

mas

Mai

wal

d, T

hom

as F

rahm

, Jen

s Ti

mm

er, U

rsul

a K

ling

mue

ller

BS06

L

ocal

mod

el f

or n

eutr

ophi

l gra

dien

t sen

sing

and

pol

ariz

atio

nM

atth

ew O

nsum

, Chr

isto

pher

V. R

ao

BS07

T

he y

east

map

Mar

cus

Kra

ntz,

Ste

fan

Hoh

man

n, H

iroa

ki K

itan

o

BS08

M

odel

ling

the

yeas

t MA

P-K

inas

e ne

twor

kC

arl-

Fre

drik

Tig

er, M

arcu

s K

rant

z, S

tefa

n H

ohm

ann,

Hir

oaki

Kit

ano

BS09

M

onit

orin

g M

AP

K o

smo-

sign

alin

g in

indi

vidu

al y

east

cel

lsD

ale

Muz

zey,

Car

los

A. G

omez

-Uri

be, J

erom

e T.

Met

teta

l, A

lexa

nder

van

Oud

enaa

rden

BS10

E

xper

imen

tal a

naly

sis

and

quan

tita

tive

mod

elin

g of

inte

ract

ions

bet

wee

n se

roto

nin

rece

ptor

sig

nali

ng p

athw

ays

Chi

ung-

wen

Cha

ng, R

avi I

yeng

ar, H

arel

Wei

nste

in

BS11

H

MG

B1

asso

ciat

ed in

trac

ellu

lar

netw

ork

Xia

o P

eng,

Kam

-Len

Dan

iel L

ee, C

hi-H

ung

Tzan

g, Q

i Zha

ng, M

eng-

Su Y

ang

BS12

M

odel

-bas

ed r

eal-

tim

e an

alys

is a

nd in

sil

ico

para

met

er id

enti

fica

tion

of

Jak/

STA

T s

igna

l tr

ansd

ucti

on in

sin

gle

cell

sM

arti

n M

onni

gman

n, D

irk

Eng

el, A

ndre

as H

errm

ann,

Mic

hael

Vog

t,

Pet

er C

. Hei

nric

h, G

erha

rd M

uell

er-N

ewen

BS13

Ly

soph

osph

atid

ylch

olin

e st

imul

ates

incr

ease

d le

vel o

f tr

ansc

ript

of

proi

nflam

mat

ory

gene

s in

mac

roph

ages

Jann

e O

estv

ang,

Han

s-R

icha

rdt B

ratt

bakk

, Sju

r H

useb

y, M

ette

Lan

gaas

, A

stri

d L

aegr

eid,

Ber

it J

ohan

sen

BS14

A

t the

inte

rfac

e of

exp

erim

ent a

nd th

eory

: cen

tral

mec

hani

sms

of T

ype

1 T-

cell

diff

eren

tiatio

nE

dda

Schu

lz, A

ndre

as R

adbr

uch,

Tho

mas

Hoe

fer

BS15

S

yste

ms

biol

ogy

of g

astr

oint

esti

nal t

umou

r bi

olog

y -

stud

ies

of g

astr

in m

edia

ted

regu

lati

on o

f ge

ne e

xpre

ssio

nTo

nje

S. S

teig

edal

, Tor

unn

Bru

land

, Ber

it D

oset

h E

itre

m, E

ndre

And

erss

en,

Liv

Tho

mm

esen

, Ast

rid

Lae

grei

d

BS16

G

loba

l gen

e ex

pres

sion

in H

EK

293

cel

ls w

ith

cont

roll

able

IC

ER

I o

r IIγ

over

expr

essi

onK

rist

ine

Mis

und,

Sun

niva

Hoe

l, T

orun

n B

rula

nd, E

ndre

And

erss

en, A

stri

d L

aegr

eid,

L

iv T

hom

mes

en

BS17

M

odel

ling

of n

egat

ive

feed

back

loop

s re

gula

ting

the

JAK

2/ST

AT

5 si

gnal

tran

sduc

tion

path

way

Juli

e B

achm

ann,

Chr

isti

an F

leck

, Tho

mas

Mai

wal

d, J

ulio

Ver

a G

onza

lez,

O

laf W

olke

nhau

er, J

ens

Tim

mer

, Urs

ula

Kli

ngm

uell

er

BS18

A

lter

ed d

ynam

ic b

ehav

ior

of th

e JA

K2/

STA

T5

sign

alin

g pa

thw

ay b

y S

TAT

5 ov

erex

pres

sion

And

rea

C. P

feife

r, C

hris

tian

Fle

ck, J

ens

Tim

mer

, Urs

ula

Kli

ngm

uell

er

BS19

C

ompu

tati

onal

mod

elin

g of

the

MC

F-7

Erb

B s

igna

ling

net

wor

k an

d an

alys

is o

f li

gand

-de

pend

ent r

espo

nses

Mar

c R

. Bir

twis

tle,

Mar

iko

Hat

akey

ama,

Nor

iko

Yum

oto,

Bab

atun

de A

. Ogu

nnai

ke,

Jan

B. H

oek,

Bor

is N

. Kho

lode

nko

BS20

Fo

rmal

des

crip

tion

of

NF

- κB

pat

hway

, its

rol

e in

apo

ptos

is, c

arci

noge

nesi

s, in

flam

mat

ion

and

way

s of

its

inac

tivat

ion

for

pred

icti

on o

f ne

w ta

rget

s fo

r an

ti-c

ance

r an

d an

ti-

infl

amm

ator

y th

erap

yR

usla

n N

. Sha

ripo

v, A

lla

F. K

olpa

kova

, Fed

or A

. Kol

pako

v

38

BS21

S

caff

old

prot

eins

con

fer

dive

rse

regu

lato

ry p

rope

rtie

s to

pro

tein

kin

ase

casc

ades

Jaso

n L

ocas

ale,

And

rey

Shaw

, Aru

p C

hakr

abor

ty

BS22

O

ptim

al in

form

atio

n pr

oces

sing

in s

mal

l sto

chas

tic

bioc

hem

ical

net

wor

ksIl

ya N

emen

man

, Man

uel J

Mid

dend

orf,

Eta

y Z

iv, C

hris

H W

iggi

ns

BS23

R

espo

nse

of a

rob

ust s

igna

ling

net

wor

k ag

ains

t tar

gete

d pe

rtur

bati

ons

Dhi

raj K

umar

, Shi

lpi J

ayas

wal

, Kan

ury

VS

Rao

BS24

M

AP

K s

igna

ling

net

wor

k pr

oper

ties

giv

ing

rise

to s

peci

fic

cell

ular

fat

e de

cisi

ons

Silv

ia S

anto

s, P

hili

ppe

Bas

tiae

ns

BS25

P

reci

se a

dapt

atio

n in

bac

teri

al c

hem

otax

is th

roug

h "a

ssis

tanc

e ne

ighb

orho

ods"

Rob

ert E

ndre

s, N

ed W

ingr

een

BS26

H

olis

tic

anal

ysis

of

epid

erm

al g

row

th f

acto

r re

cept

or s

igna

ling

pat

hway

Sali

ha D

urm

us, K

. Yal

cin

Arg

a, K

utlu

O. U

lgen

BS27

G

ene

expr

essi

on d

ata

to d

eter

min

e si

gnal

ing

path

way

s fo

r cu

tane

ous

chem

ical

irri

tati

onJa

mes

N. M

cDou

gal

BS28

F

GF

sig

nali

ng n

etw

ork

mod

el in

clud

ing

mul

tipl

e ce

llul

ar c

ompa

rtm

ents

Tats

unor

i Nis

him

ura,

Mas

aru

Tate

no

BS29

E

luci

dati

on o

f th

e hi

dden

dyn

amic

fea

ture

s in

the

ER

K p

athw

ayD

ongs

an K

im, K

wan

g-H

yun

Cho

BS30

E

ndoc

ytos

is a

nd s

igna

ling

: com

peti

tion

of

Rab

pro

tein

s fo

r m

aint

enan

ce a

nd c

atas

trop

he

of s

ubce

llul

ar c

ompa

rtm

ents

Per

la D

el C

onte

-Zer

ial,

Lut

z B

rusc

h, C

laud

io C

olli

net,

Joc

hen

Rin

k,

Yann

is K

alai

dzid

is, A

ndre

as D

euts

ch, M

arin

o Z

eria

l

BS31

E

luci

dati

ng th

e fr

eque

ncy-

deco

ding

mec

hani

sm f

or d

iffe

rent

ial g

onad

otro

pic

subu

nit

gene

exp

ress

ion

Stef

an L

im, Y

u-K

ai T

he, S

ihui

Wan

g, G

unar

etna

m R

ajag

opal

, Phi

lipp

a M

elam

ed

BS32

S

tabi

lity

and

kin

etic

s of

the

TG

F-b

eta

path

way

Pon

tus

Mel

ke, H

enri

k Jo

nsso

n, E

vang

elia

Par

dali

, Pet

er te

n D

ijke

, Car

sten

Pet

erso

n

BS35

U

nder

stan

ding

the

prin

cipl

es o

f th

e co

mpu

tati

onal

pro

cess

per

form

ed b

y is

ofor

ms

in

MA

P k

inas

e ca

scad

eC

elli

na C

ohen

-Sai

don,

Ari

el C

ohen

, Ale

xand

er S

igal

, Nat

alie

Per

zov,

Tam

ar D

anon

, U

ri A

lon

BS36

A

mod

elin

g te

chni

que

base

d on

tran

sfer

fun

ctio

n fo

r bi

olog

ical

sys

tem

s an

d it

s ap

plic

atio

n to

MA

PK

sig

nal t

rans

duct

ion

Taka

shi N

akak

uki,

Nor

iko

Yum

oto,

Tak

ashi

Nak

a, M

arik

o H

atak

eyam

a

BS37

Q

uant

itat

ive

anal

ysis

of

dose

- an

d ti

me-

depe

nden

t ear

ly tr

ansc

ript

ion

cont

roll

ed b

y R

TK

-m

edia

ted

sign

al tr

ansd

ucti

on p

athw

ays

Take

shi N

agas

him

a, H

idet

oshi

Shi

mod

aira

, Kao

ri I

de, T

akas

hi N

akak

uki,

Yu

kita

ka T

ani,

Mar

iko

Hat

akey

ama

BS38

B

iopa

th -

a n

ew a

ppro

ach

to f

orm

al d

escr

ipti

on a

nd s

imul

atio

n of

com

plex

bio

logi

cal

syst

ems

and

proc

esse

sF

edor

Kol

pako

v, R

usla

n Sh

arip

ov, E

kate

rina

Kal

ashn

ikov

a, E

lena

Che

rem

ushk

ina

BS39

T

hres

hold

s in

tran

sien

t dyn

amic

s of

sig

nal t

rans

duct

ion

path

way

sK

atja

Rat

eits

chak

, Ola

f Wol

kenh

auer

BS40

A

com

puta

tion

al m

odel

of T

ype

I in

terf

eron

rec

epto

r si

gnal

ing

path

way

Ivan

Mar

tine

z-F

orer

o, J

aim

e Ir

anzo

, Jor

ge E

lorz

a, P

ablo

Vil

losl

ada

Syst

ems

Bio

logy

for

Med

icin

eSy

stem

s B

iolo

gy f

or D

rug

Dis

cove

ry

MR0

1 A

com

puta

tion

al d

rug

targ

et a

nd d

rug

scre

enin

g pi

peli

neX

ingh

ua S

hi, F

ang

fang

Xia

, Ric

k St

even

s

MR0

2 D

rug

disc

over

y in

sm

all m

olec

ule

met

abol

ic s

pace

Cor

ey A

dam

s, M

ike

Kei

ser,

Pat

rici

a B

abbi

tt, B

rian

Sho

iche

t

MR0

3 F

low

cyt

omet

ric

anal

ysis

and

cyt

otox

icit

y as

say

of e

xtra

cts

of A

stro

dauc

us P

ersi

cus

in

com

pari

son

to D

oxor

ubic

in in

hum

an b

reas

t can

cer T

47D

cel

lsE

brah

im A

zizi

, Moh

amm

adho

ssei

n A

bdol

moh

amm

adi,

Sha

mil

eh F

oula

ddel

, G

hola

mre

za A

min

, Abb

as S

hafie

e

MR0

4 G

enet

ic s

ynth

etic

leth

alit

y sc

reen

ing

by s

hRN

A-m

edia

ted

RN

A in

terf

eren

ce to

olYu

lia

Ein

av, R

euve

n A

gam

i, D

an C

anaa

ni

MR0

5 In

sil

ico

anal

ysis

of

vibr

io v

ulni

ficus

CM

CP

6 m

etab

olis

m f

or th

e fa

cili

tate

d dr

ug ta

rget

ing

Hyu

n U

k K

im, T

ae Y

ong

Kim

, Kw

angj

oon

Jeon

g, S

oo Y

oung

Kim

, Joo

n H

aeng

Rhe

e,

Sang

Yup

Lee

MR0

7 O

ne e

nzym

e ca

n gi

ve b

oth

enan

tiom

ers

Yosu

ke T

erao

, Ken

ji M

iyam

oto,

Hir

omic

hi O

hta

MR0

8 G

enom

e-w

ide

biol

ogic

al r

espo

nse

fing

erpr

inti

ng (

Bio

ReF

) of

trad

itio

nal C

hine

se

med

icin

e fo

rmul

a IS

F-1

rev

eals

a p

oten

tial

rol

e of

hem

e ox

ygen

ase-

1 pa

thw

ay in

the

anti

oxid

ant t

hera

pyJi

anhu

i Ron

g, C

ynth

ie Y

im-H

ing

Che

ung,

Jia

ngan

g Sh

en, P

aul K

won

g-H

ang

Tam

, A

llan

Sik

-Yin

Lau

Car

diov

ascu

lar

Syst

ems

Bio

logy

MV0

1 Id

enti

fica

tion

and

inte

grat

ive

anal

ysis

of

nove

l gen

es w

ith

card

iac

expr

essi

on in

mou

seIn

ju P

ark,

Hoy

ong

Lee

, Tae

wan

Kim

, Do

Han

Kim

, Chu

nghe

e C

ho

MV0

2 D

ynam

ical

ana

lysi

s of

bet

a-ad

rene

rgic

sig

nali

ng p

athw

ays

in c

ardi

ac m

yocy

tes

Sung

-You

ng S

hin,

Won

-Sun

g B

ae, T

ae-H

wan

Kim

, San

g-M

ok C

hoo,

Kw

ang-

Hyu

n C

ho

MV0

3 M

easu

rem

ent o

f ca

lcin

euri

n ac

tivit

y in

HL

-1 c

ell l

ine

by c

apil

lary

ele

ctro

phor

esis

Shei

kh M

d. E

naye

tul B

abar

, Eun

Joo

Son

g, Y

oung

Soo

k Yo

o

MV0

4 A

com

pute

r m

odel

of

beta

1-ad

rene

rgic

sig

nali

ng c

asca

de in

car

diac

myo

cyte

Mas

anor

i Kuz

umot

o, S

atos

hi M

atsu

oka,

Aki

nori

Nom

a

MV0

5 Im

pact

of

a no

n-ge

nom

ic p

athw

ay o

n Q

T in

terv

als

shor

teni

ng b

y te

stos

tero

ne: M

echa

nism

of

sex

-rel

ated

dif

fere

nce

in f

atal

arr

hyth

mia

sJu

nko

Kur

okaw

a, C

hang

-Xi B

ai, T

etsu

shi F

uruk

awa

39

MV0

6 A

nut

rige

nom

ics

appr

oach

to d

efine

a “

life

styl

e al

gori

thm

” to

be

used

in c

hron

ic d

isea

se

prev

enti

on, d

iagn

osis

and

ther

apy.

Inge

rid

Arb

o, H

ans-

Ric

hard

Bra

ttba

kk, S

iv A

agaa

rd, A

nn K

rist

in D

e So

ysa,

In

ge L

inds

eth,

Fed

on L

indb

erg,

Met

te L

anga

as, E

ndre

And

erss

en, B

ard

Kul

seng

, B

erit

Joh

anse

n

MV0

7 M

athe

mat

ical

mod

els

of li

popr

otei

n m

etab

olis

mB

rend

an O

'Mal

ley,

J. P

anov

ska,

M T

inda

ll, L

. War

e, L

Pic

kers

gill

, J K

ing

MV0

8 G

enet

ic a

naly

sis

of th

e ca

lciu

m s

igna

lsom

e in

hea

rt a

nd id

enti

fica

tion

of

mol

ecul

ar h

ubs

invo

lved

in h

eart

fai

lure

Josh

ua S

ung

Woo

Yan

g, Y

ong

Il Y

oum

, In-

Sun

Chu

MV0

9 P

rote

in in

tera

ctio

n ne

twor

k in

E-C

cou

plin

gG

il B

u K

ang,

Jun

Hyu

ck L

ee, M

un-K

youn

g K

im, S

ung

Hyu

n K

im, S

oo H

yun

Eom

MV1

0 C

ompe

nsat

ory

chan

ges

in th

e ac

tivit

y of

gen

etic

net

wor

k of

cal

cium

sig

nall

ing

com

pone

nts

in r

espo

nse

to d

rug-

indu

ced

pert

urba

tion

s of

cal

cium

hom

eost

asis

Youn

g Il

Yeo

m, S

o C

hon

Han

, Jos

hua

Sung

Woo

Yan

g, S

eong

-Min

Par

k, I

n Su

n C

hu

MV1

1 A

nti-

prol

ifer

ativ

e ef

fect

s of

rat

aor

tic

smoo

th m

uscl

e ce

lls

by b

erap

rost

, a P

GI2

ana

logu

e,

thro

ugh

the

indu

ctio

n of

PPA

R-d

elta

and

its

dow

nstr

eam

eff

ecto

r of

iNO

SSh

u-H

ui J

uan,

Ja-

Lin

g L

ee, H

eng

Lin

MV1

2 P

rote

omic

and

met

abol

omic

ana

lysi

s of

HL

-1 c

ardi

omyo

cyte

sE

un J

oo S

ong,

Byu

ng H

wa

Jung

, Bon

g C

hul C

hung

, You

ng S

ook

Yoo

MV1

3 A

con

stru

ctio

n of

larg

e-sc

ale

prot

ein-

prot

ein

inte

ract

ion

netw

ork

of c

alci

um s

igna

ling

pa

thw

ay in

myo

card

ial m

uscl

e sy

stem

and

its

vali

dati

on b

y us

ing

mas

s sp

ectr

omet

ry

base

d hi

gh th

roug

hput

pro

teom

e an

alys

is te

chni

ques

Hye

jin

Song

, Hye

kyun

g K

won

, Zee

-Yon

g P

ark

MV1

4 In

tegr

ated

app

roac

h fo

r si

mul

atio

n of

phy

siol

ogic

al, b

iom

echa

nica

l, an

d m

olec

ular

-ge

neti

cal a

spec

ts o

f ar

teri

al h

yper

tens

ioin

Fedo

r A

. Kol

pako

v, R

usla

n N

. Sha

ripo

v, E

lina

A. B

iber

dorf

, Yur

iy L

. Tra

khin

in,

Mik

hail

V. P

uzan

ov, A

lexa

nder

V. K

oshu

kov,

Ale

xand

er M

. Blo

khin

, Ark

adiy

L. M

arke

l, L

udm

ila

N. I

vano

va

MV1

5 A

ntih

yper

tens

ive

and

endo

thel

inpr

otec

tive

effi

cien

cy o

f at

orva

stat

in a

nd n

ebiv

olol

co

mbi

nati

on in

pat

ient

s w

ith

esse

ntia

l hyp

erte

nsio

nYu

liya

Sha

posh

niko

va

MV1

6 T

heor

etic

al a

naly

sis

of o

xyge

n tr

ansp

ort a

nd N

O d

iffu

sion

insi

de m

icro

vasc

ulat

ure

Ken

ta Y

ashi

ma,

Kot

aro

Oka

MV1

7 H

CN

et: a

n in

tegr

ated

dat

abas

e of

hea

rt a

nd c

alci

um f

unct

iona

l net

wor

ks f

or s

yste

ms

biol

ogy

Seon

g-H

wan

Rho

, Seo

ng-E

ui H

ong,

Do

Han

Kim

MV1

8 E

luci

dati

on o

f a

pote

ntia

l fra

nk-s

tarl

ing

mec

hani

sm th

roug

h m

odel

ing

and

sim

ulat

ion

Nat

alie

S. S

chne

ider

, Tak

ao S

him

ayos

hi, A

kira

Am

ano,

Tet

suya

Mat

suda

MV1

9 C

hara

cter

isti

cs o

f lo

cal a

nd f

ocal

Ca2

+ s

igna

ling

in c

ardi

omyo

cyte

cel

l lin

e H

L-1

Yuhu

a L

i, M

in-J

eong

Son

, Sun

woo

Lee

, Le

Thi

Thu

, Do

Han

Kim

, Jou

ng R

eal A

hn,

Sun-

Hee

Woo

MV2

0 C

ompu

tati

onal

app

roac

hes

for

regu

lati

on o

f L

-typ

e ca

lciu

m c

hann

el b

y ph

osph

oryl

atio

n in

car

diac

myo

cyte

sM

asay

uki T

akah

ashi

, Ken

ta Y

ashi

ma,

Koh

ji H

otta

, Kot

aro

Oka

MV2

1 A

ntii

sche

mic

effi

cien

cy o

f at

orva

stat

in in

the

pati

ents

wit

h is

chem

ic h

eart

dis

ease

sYu

liya

Sha

posh

niko

va, V

era

Shko

lnik

Syst

ems

Imm

unol

ogy

MI0

1 S

truc

tura

l ana

lysi

s of

the

T-ce

ll-r

ecep

tor-

indu

ced

sign

alin

g ne

twor

kJu

lio

Saez

-Rod

rigu

ez, L

uca

Sim

eoni

, Jon

atha

n L

indq

uist

, Reb

ecca

Hem

enw

ay,

Urs

ula

Bom

mha

rdt,

Bor

ge A

rndt

, Utz

-Uw

e H

aus,

Rob

ert W

eism

ante

l,

Ern

st D

iete

r G

ille

s, S

teff

en K

lam

t, B

urkh

art S

chra

ven

MI0

2 M

odel

ing

chan

ges

in I

kB a

nd N

F-k

B a

ctiv

atio

n in

mac

roph

ages

trea

ted

wit

h di

chlo

ropr

opio

nani

line

John

B. B

arne

tt, I

rina

V. U

styu

gova

, Dav

id K

link

e, K

athl

een

Bru

ndag

e, T

hom

as M

. Har

ty

MI0

3 M

icro

arra

y an

alys

is c

hara

cter

izes

gen

e re

gula

tion

in h

uman

ast

rocy

tes

follo

win

g D

NA

da

mag

eJu

n-ic

hi S

atoh

, Hir

oko

Tabu

noki

MI0

4 C

hara

cter

izat

ion

of th

e cl

eava

ge o

f si

gnal

pep

tide

at t

he C

-ter

min

us o

f he

pati

tis

C v

irus

co

re p

rote

in b

y si

gnal

pep

tide

pep

tida

seH

sin-

Chi

eh M

a, Y

i-Yu

ng K

u, Y

i-C

hing

Hsi

eh, S

hih-

Yen

Lo

MI0

5 In

ter-

indi

vidu

al p

rote

omic

pro

fili

ng o

f bl

ood

mon

ocyt

es r

evea

ls b

iolo

gica

l ins

ight

sH

aife

ng W

u, P

hili

p D

iaz,

Min

g Ji

n

MI0

6 M

odel

ing

the

infl

uenc

e of

dia

bati

c gl

ucos

e co

ncen

trat

ion

on n

eutr

ophi

l act

ivat

ion

Urs

ula

Kum

mer

, Jen

s C

hris

tian

Bra

sen

MI0

7 E

luci

dati

ng th

e m

olec

ular

reg

ulat

ion

of g

anod

erm

a lu

cidu

m p

olys

acch

arid

es in

hum

an

mon

ocyt

ic c

ells

: fro

m g

ene

expr

essi

on to

net

wor

k co

nstr

ucti

onH

sueh

-Fen

Jua

n, K

un-C

hieh

Che

ng, H

suan

-Che

ng H

uang

, Che

rn-H

an O

u,

Jenn

-Han

Che

n, W

en-B

in Y

ang,

Shu

i-Te

in C

hen,

Chi

-Hue

y W

ong

MI0

8 C

oexp

ress

ion

netw

orks

for

mac

roph

ages

init

iate

d by

two

mem

bers

of

the

TN

F li

gand

su

perf

amily

.R

ajee

v A

uror

a, J

enni

fer

Kie

sel,

Ran

gesh

Kun

nava

kam

, You

sef A

bu-A

mer

MI0

9 Pr

even

tion

of f

etal

loss

due

to s

yste

mic

infla

mm

atio

n an

d an

ti-ph

osph

olip

id a

ntib

odie

s by

D

6Ye

ny M

arti

nez

de la

Tor

re, C

hiar

a B

urac

chi,

Ele

na M

. Bor

roni

, Raf

fael

la B

onec

chi,

M

anue

la N

ebul

oni,

Fra

nces

co T

edes

co, S

ergi

o A

. Lir

a, A

nnun

ciat

a V

ecch

i,

Mas

sim

o L

ocat

i, A

lber

to M

anto

vani

MI1

0 A

gen

etic

sw

itch

in h

uman

cel

ls e

luci

date

d by

"sy

stem

s vi

rolo

gy"

Mar

ia W

erne

r, J

ieZ

hi Z

ou, J

enny

Alm

qvis

t, I

ngem

ar E

rnbe

rg, E

rik

Aur

ell

40

Syst

ems

Bio

logy

of

Dia

bete

s (N

ovo

Nor

disk

-spo

nsor

ed)

MD0

1 T

he id

enti

fica

tion

of

new

nov

el b

iom

arke

rs o

f di

seas

e an

d to

xici

ty u

sing

UP

LC

/MS

e an

d ad

vanc

ed m

ulti

Rob

ert P

lum

b, J

erem

oy N

icho

lson

, Ian

Wil

son,

Pau

l Rai

nvil

le

MD0

2 H

∞ c

ontr

olle

r de

sign

for

glu

cose

-ins

ulin

sys

tem

s: a

BM

I op

tim

izat

ion

appr

oach

Che

ng-L

iang

Che

n, H

ong-

Wen

Tsa

i

MD0

3 Q

uali

tativ

e, in

tegr

ated

mod

elin

g of

lipi

d m

etab

olis

m in

hep

atoc

ytes

Ovi

diu

Rad

ules

cu, A

nne

Sieg

el, M

iche

l Le

Bor

gne,

Phi

lipp

e V

eber

, Eli

sabe

th P

ecou

, Sa

ndri

ne L

agar

rigu

e, P

asca

l Mar

tin

MD0

4 St

udy

of d

epen

denc

y of

syn

chro

niza

tion

of b

eta-

cells

insu

lin s

ecre

tion

on s

ize

of la

nger

hans

is

lets

Ari

osto

Siq

ueir

a Si

lva,

Jos

e A

ndre

s Yun

es

MD0

5 D

iabe

tes

man

agem

ent s

yste

m b

ased

on

syst

ems

biol

ogy

aim

ed a

t off

erin

g a

ther

apeu

tic

stra

tegy

for

eac

h pa

tien

tM

asay

oshi

Sei

ke, T

akeo

Sai

tou,

Yas

uhir

o K

ouch

i, K

aoru

Asa

no, T

akes

hi O

hara

, Ya

suhi

ro N

aito

, Hir

omu

Nak

ajim

a

MD0

6 Id

enti

fica

tion

of

the

spec

ific

geno

mic

and

pro

teom

ic m

arke

rs in

Str

epto

zoto

cin-

indu

ced

diab

etic

rat

pan

crea

s in

res

pons

e to

fun

gal p

olys

acch

arid

e tr

eatm

ents

Sang

Woo

Kim

, Hye

Jin

Hw

ang,

Jun

g Yo

ung

Oh,

Eun

Jae

Cho

, Yu

Mi B

aek,

Jo

ng W

on Y

un

MD0

7 T

ime-

depe

nden

t pla

sma

prot

ein

chan

ges

in s

trep

tozo

toci

n-in

duce

d di

abet

ic r

ats

in

resp

onse

to f

unga

l pol

ysac

char

ide

trea

tmen

tsSa

ng W

oo K

im, H

ye J

in H

wan

g, E

un J

ae C

ho, J

ung

Youn

g O

h, Y

u M

i Bae

k,

Jong

Won

Yun

MD0

8 G

ene

expr

essi

on p

rofi

ling

in s

trep

tozo

toci

n-in

duce

d di

abet

ic r

at li

ver

and

kidn

ey in

re

spon

se to

fun

gal p

olys

acch

arid

e th

erap

yH

ye J

in H

wan

g, S

ang

Woo

Kim

, Eun

Jae

Cho

, Jun

g Yo

ung

Oh,

Yu

Mi B

aek,

Jo

ng W

on Y

un

MD0

9 D

iffe

rent

ial e

xpre

ssio

n of

the

kidn

ey p

rote

ins

in s

trep

tozo

toci

n-in

duce

d di

abet

ic r

ats

befo

re a

nd a

fter

adm

inis

trat

ion

of f

unga

l pol

ysac

char

ides

Hye

Jin

Hw

ang,

San

g W

oo K

im, E

un J

ae C

ho, J

ung

Youn

g O

h, Y

u M

i Bae

k,

Jong

Won

Yun

Can

cer

Syst

ems

Bio

logy

MC0

1 M

odel

ing

of th

e es

trog

en r

ecep

tor-

regu

late

d pr

otei

n ne

twor

k in

bre

ast c

ance

rO

zgur

Sah

in, F

lori

an H

ahne

, Tim

Bei

ssba

rth,

Ann

emar

ie P

oust

ka, S

tefa

n W

iem

ann,

D

orit

Arl

t

MC0

2 O

n th

e ro

le o

f bi

omec

hani

cs in

the

grow

th o

f m

ulti

cell

ular

sph

eroi

dsD

irk

Dra

sdo,

Ste

fan

Hoe

hme

MC0

3 S

tudy

of

earl

y tu

mou

r de

velo

pmen

t and

its

glyc

olyt

ic p

rope

rtie

sA

rios

to S

ique

ira

Silv

a, J

ose

And

res Y

unes

MC0

4 A

ppli

cati

ons

of s

ensi

tivit

y an

alys

is f

or d

rug

disc

over

y an

d de

velo

pmen

t in

the

Erb

B

rece

ptor

net

wor

kB

rian

Har

ms,

All

en L

ee, R

icar

do P

axso

n, U

lrik

Nie

lsen

, Bir

git S

choe

berl

MC0

5 D

elin

eati

ng b

reas

t can

cer

gene

exp

ress

ion

syst

ems

by R

NA

inte

rfer

ence

and

glo

bal

mic

roar

ray

anal

ysis

in h

uman

tum

or c

ells

Hol

ger

Sult

man

n, M

ark

Fell

man

n, A

ndre

as B

unes

s, M

arku

s R

usch

haup

t, A

chim

Tre

sch,

Ti

m B

eiss

bart

h, R

upre

cht K

uner

, Ann

emar

ie P

oust

ka

MC0

6 S

yste

ms-

leve

l mec

hani

sms

of tu

mor

igen

esis

Pil

ar H

erna

ndez

, Jai

me

Hue

rta-

Cep

as, D

avid

Mon

tane

r, Fa

tim

a A

l-Sh

ahro

ur, J

oan

Vall

s,

Lai

a G

omez

, Gab

riel

Cap

ella

, Joa

quin

Dop

azo,

Miq

uel A

ngel

Puj

ana

MC0

7 Sy

stem

atic

dis

cove

ry o

f ca

ndid

ate

gene

tic in

tera

ctio

ns le

adin

g to

bre

ast c

ance

r su

scep

tibili

tyM

ikke

l Zah

le O

este

rgaa

rd, J

onat

han

Tyre

r, B

ruce

AJ

Pond

er, D

ougl

as F

Eas

ton,

F

rede

rick

Rot

h, P

aul D

P P

haro

ah

MC0

8 M

eta-

anal

ysis

of

brea

st c

ance

r m

icro

arra

y da

ta: r

elia

ble

iden

tifi

cati

on o

f up

- an

d do

wn-

regu

late

d ge

nes

Yuri

y V.

Kon

drak

hin,

Vla

dim

ir V

. Por

oiko

v, R

usla

n N

. Sha

ripo

v, A

lexa

nder

E. K

el,

Fedo

r A

. Kol

pako

v

MC0

9 C

yclo

net -

an

inte

grat

ed d

atab

ase

on c

ell c

ycle

reg

ulat

ion

and

carc

inog

enes

isFe

dor

Kol

pako

v, V

ladi

mir

Por

oiko

v, R

usla

n Sh

arip

ov, L

ucia

no M

ilan

esi,

Ale

xand

er K

el

MC1

0 M

etab

olic

cha

nges

dur

ing

carc

inog

enes

is: p

oten

tial

impa

ct o

n in

vasi

vene

ssK

iera

n Sm

allb

one,

Rob

ert A

. Gat

enby

, Rob

ert J

. Gil

lies

, Dav

id J

. Gav

agha

n,

Phi

lip

K. M

aini

MC1

1 Te

mpo

ral g

ene

expr

essi

on p

rofi

ling

app

lied

to th

e hy

poxi

c re

spon

seR

enau

d Se

igne

uric

, Mau

d St

arm

ans,

Mic

hael

Mag

agni

n, N

atal

Van

Rie

l, B

rad

Wou

ters

, P

hili

ppe

Lam

bin

MC1

2 M

AP-

kina

se s

igna

ling

in e

ryth

roid

pro

geni

tor

cells

elu

cida

ted

by a

dyn

amic

pat

hway

mod

elM

arce

l Sch

illi

ng, T

hom

as M

aiw

ald,

Jen

s Ti

mm

er, U

rsul

a K

ling

mue

ller

MC1

3 M

icro

RN

A e

xpre

ssio

n pr

ofili

ng o

f he

pato

cell

ular

car

cino

ma

usin

g m

icro

arra

yH

isak

azu

Iwam

a, T

suto

mu

Mas

aki,

Shi

geki

Kur

iyam

a

Fro

nts

in S

yste

ms

Bio

logy

Net

wor

k B

iolo

gy

FN01

E

volu

tion

ary

cons

erva

tion

of

dyna

mic

pro

tein

-pro

tein

inte

ract

ion

netw

orks

Che

n-hs

iung

Cha

n, S

heng

-An

Lee

, Che

ng-Y

an K

ao

FN02

C

orre

lati

on a

nd r

espo

nse

of a

sto

chas

tic

gene

sw

itch

Yuri

e O

kabe

, Yuu

Yag

i, M

asak

i Sas

ai

FN03

D

esig

n pr

inci

ples

in E

. col

i tra

nscr

ipti

on n

etw

ork

reve

aled

by

usin

g a

com

preh

ensi

ve

libr

ary

of fl

uore

scen

t tra

nscr

ipti

onal

rep

orte

rsA

lon

Zas

lave

r, A

nat B

ren,

Mic

hal R

onen

, Sha

lev

Itzk

ovit

z, I

lya

Kik

oin,

Sea

gull

Sha

vit,

W

olfr

am L

iebe

rmei

ster

, Mik

e Su

rett

e, U

ri A

lon

41

FN04

N

etw

ork

iden

tifi

cati

on f

or th

e G

1 to

S tr

ansi

tion

in m

amm

alia

n ce

lls

Luc

iano

Mil

anes

i, Fe

rdin

ando

Chi

arad

onna

, Rob

erta

Alfi

eri,

Dan

iela

Gag

lio,

M

arco

Van

oni,

Lil

ia A

lber

ghin

a

FN05

L

ogic

of

tran

scri

ptio

nal c

ircu

its

unde

rlyi

ng m

amm

alia

n ci

rcad

ian

cloc

ksM

aki U

kai-

Tade

num

a, H

irok

i R. U

eda

FN06

N

etw

ork

cond

itio

ns f

or in

stab

ilit

ies

in b

ioch

emic

al m

odel

sM

aya

Min

chev

a

FN08

A

ste

pwis

e st

ruct

ural

equ

atio

n m

odel

ing

algo

rith

m to

pre

dict

gen

etic

net

wor

ksG

race

Shw

u-R

ong

Shie

h, C

hing

-Yun

Yu,

Chu

ng-M

ing

Che

n, J

uili

ng H

uang

, W

oei-

Fuh

Wan

g

FN09

Pa

tter

n re

cogn

itio

n m

etho

d fo

r in

ferr

ing

of g

enet

ic n

etw

orks

Gra

ce S

hwu-

Ron

g Sh

ieh,

Che

ng-L

ong

Chu

ang,

Chu

ng-M

ing

Che

ng

FN10

A

hyb

rid

sim

ulat

ion

fram

ewor

k fo

r ge

nom

e sc

ale

stud

y of

mol

ecul

ar d

ynam

ics

in

Esc

heri

chia

col

iSa

mik

Gho

sh, P

reet

am G

hosh

, Kal

yan

Bas

u, S

ajal

K. D

as

FN11

R

econ

stru

ctio

n of

the

hum

an m

etab

olic

net

wor

k an

d it

s re

lati

on w

ith

hum

an d

isea

seH

ong

wu

Ma,

Ana

toly

Sor

okin

, Ale

x Se

lkov

, Evg

eni S

elko

v, S

haki

r A

li,

Ale

xand

er M

azei

n, S

aow

alak

Kal

apan

ulak

, Ole

g D

emin

, Igo

r G

orya

nin

FN12

Fi

ndin

g pe

rtur

bati

on-s

peci

fic

regu

lati

on p

athw

ays

by in

tegr

atin

g ge

neti

c re

gula

tory

and

m

etab

olic

pat

hway

Ho

Jung

Nam

, Hyo

jin

Kan

g, S

ejun

Lee

, Doh

eon

Lee

FN13

H

ighl

y co

rrel

ated

gro

ups

of m

ulti

ple

gene

s an

d/or

met

abol

ites

in A

rabi

dops

is th

alia

na

dete

cted

by

grap

h cl

uste

ring

(D

PC

lus)

Ats

ushi

Fuk

ushi

ma,

Md.

Alt

af-U

l-A

min

, Ken

Kur

okaw

a, S

hige

hiko

Kan

aya,

M

asam

i Yok

ota

Hir

ai, K

azuk

i Sai

to

FN14

T

rans

crip

tion

al r

egul

atio

n of

the

abio

tic

stre

ss r

espo

nse

in A

rabi

dops

isD

anie

l Mac

Lea

n, N

oah

Whi

tman

, Chr

is W

ilks

, Seu

ng Y

on R

hee

FN15

P

heno

typi

c co

mpl

exit

y du

ring

C. e

lega

ns e

arly

em

bryo

gene

sis

and

syst

emat

ic

imte

rpre

tati

on o

f pl

eiot

ropy

wit

h pr

otei

n in

tera

ctio

n ne

twor

ksL

ihua

Zou

, Bri

an R

oss,

Jun

Liu

, Hui

Ge

FN16

S

toch

asti

c m

odel

of

a bi

olog

ical

clo

ckH

ites

h M

istr

y

FN17

M

etho

ds f

or th

e st

ruct

ural

and

fun

ctio

nal a

naly

sis

of s

igna

ling

net

wor

ksSt

effe

n K

lam

t, J

ulio

Sae

z-R

odri

guez

, Ern

st D

iete

r G

ille

s

FN18

T

he E

dinb

urgh

pat

hway

edi

tor:

a n

ovel

app

roac

h to

cre

atin

g an

d an

nota

ting

com

plex

bi

olog

ical

net

wor

ksA

nato

ly S

orok

in, A

lex

Selk

ov, S

haki

r A

li, S

tuar

t Moo

die,

Igo

r G

orya

nin

FN19

A

lgeb

raic

met

hod

for

the

anal

ysis

of

sign

alin

g cr

osst

alk

Yosh

iya

Mat

suba

ra, S

hini

chi K

ikuc

hi, M

asah

iro

Sugi

mot

o, K

otar

o O

ka, M

asar

u To

mit

a

FN20

M

axim

um e

ntro

py a

ppro

ach

to n

etw

ork

reco

nstr

ucti

onG

aspe

r T

kaci

k, E

lad

Schn

eidm

an, W

illi

am B

iale

k

FN21

P

rinc

iple

s of

mic

roR

NA

reg

ulat

ion

of a

hum

an c

ellu

lar

sign

alin

g ne

twor

kQ

ingh

ua C

ui, Z

henb

ao Y

u, E

nric

o P

uris

ima,

Edw

in W

ang

FN22

S

ignA

lign

: a to

ol f

or a

naly

sing

sig

nali

ng p

athw

ays

Srid

har

Har

ihar

aput

ran,

Tho

ralf

Toe

pel

FN23

S

et-u

p of

the

nati

onal

net

wor

k fo

r sy

stem

s bi

olog

y in

Ger

man

yU

te H

eisn

er

FN24

S

etti

ng th

e fr

amew

ork

for

larg

e sc

ale

syst

em b

iolo

gy: t

he in

tegr

atio

n of

hum

an p

rote

in

inte

ract

ome

Mat

thia

s E

. Fut

schi

k, G

auta

m C

haur

asia

, Eri

ch W

anke

r, H

ansp

eter

Her

zel

FN25

A

sys

tem

bio

logy

app

roac

h to

the

imm

une

syst

em n

etw

ork

reve

als

func

tion

al d

iffe

renc

es

in h

ealt

h an

d m

ulti

ple

scle

rosi

sP

ablo

Vil

losl

ada,

Ric

ardo

Pal

acio

s, J

oaqu

in G

oni,

Nie

ves

Vel

ez, J

orge

Sep

ulcr

e

FN26

M

odel

ing

the

extr

acel

lula

r an

d ce

ll-s

urfa

ce e

nvir

onm

ent i

mpa

ctin

g W

nt s

igna

ling

Ann

a G

eorg

ieva

, Sat

ish

Tade

pall

i, B

rian

Sto

ll

FN27

M

athe

mat

ical

mod

elli

ng o

f th

e ro

le o

f H

IF-1

in tu

mou

r gr

owth

Ale

xand

er G

. Fle

tche

r, S.

Jon

atha

n C

hapm

an, C

hris

toph

er J

. W. B

rew

ard

FN28

G

raph

theo

ry a

nd n

etw

orks

in b

iolo

gyO

live

r M

ason

, Mar

k V

erw

oerd

FN29

To

war

ds a

pro

teom

e sc

ale

map

of

the

hum

an in

tera

ctom

e ne

twor

kJe

an-F

ranc

ois

Rua

l, K

avit

ha V

enka

tesa

n, T

ong

Hao

, Tom

oko

Hir

ozan

e-K

ishi

kaw

a,

Am

elie

Dri

cot,

Nin

g L

i, G

abri

el B

erri

z, F

ranc

is G

ibbo

ns, M

atij

a D

reze

,N

ono

Ayi

vi-G

uede

hous

sou,

Nie

ls K

litg

ord,

Chr

isto

phe

Sim

on, M

ike

Box

em,

Stua

rt M

ilst

ein,

Jen

nife

r R

osen

berg

, Deb

ra S

. Gol

dber

g, L

an Z

hang

, Sh

aryl

Won

g, G

iova

nni F

rank

lin,

Sim

ing

Li,

Joa

nna

Alb

ala,

Jan

ghoo

Lim

, C

arle

ne F

raug

hton

, Est

elle

Lla

mos

as, S

ebih

a C

evik

, Cam

ille

Bex

, Phi

lipp

e L

ames

ch,

Rob

ert S

. Sik

orsk

i, J

ean

Van

denh

aute

, Hud

a Z

oghb

i, A

lex

Smol

yar,

Ste

phan

ie B

osak

, R

eyna

ldo

Sequ

erra

, Lyn

n D

ouce

tte-

Stam

m, M

icha

el E

. Cus

ick,

Dav

id E

. Hil

l,

Fre

deri

ck P

. Rot

h, M

arc

Vid

al

FN30

L

ag-a

ppen

ded

PC

A: a

new

met

hod

for

infe

rrin

g th

e ca

usal

rel

atio

nshi

p be

twee

n ge

nes

from

tem

pora

l exp

ress

ion

profi

les

Yeoi

n Yo

on, K

wan

g-H

yun

Cho

FN31

In

fere

nce

of tr

ansc

ript

iona

l reg

ulat

ory

netw

orks

bas

ed o

n in

itia

l mR

NA

exp

ress

ion

profi

les

and

DN

A-b

indi

ng m

otif

sH

youn

g-Se

ok C

hoi,

San

g-M

ok C

hoo,

Jeo

ng-R

ae K

im, K

wan

g-H

yun

Cho

FN32

M

odel

ing

and

sens

itiv

ity

anal

ysis

of

circ

adia

n os

cill

ator

y ne

twor

k of

dro

soph

ila

Yuki

no O

gaw

a, K

azuh

aru

Ara

kaw

a, F

umih

iko

Miy

oshi

, Kaz

unar

i Kai

zu,

Mas

aru

Tom

ita

FN33

A

n ev

olut

iona

ry s

yste

ms

biol

ogy

appr

oach

for

the

anal

ysis

of

the

dyna

mic

s of

red

uctiv

e ge

nom

e ev

olut

ion

Am

it K

hach

ane,

Jac

ek P

ucha

lka,

Ken

neth

Tim

mis

, Vit

or M

arti

ns d

os S

anto

s

FN34

M

essa

ge-a

djus

ted

netw

orks

(M

AN

) in

gas

tro-

ente

ro-p

ancr

eati

c (G

EP

) en

docr

ine

syst

emN

uri F

aruk

Ayk

an

42

FN35

R

ever

se e

ngin

eeri

ng b

iolo

gica

l net

wor

ks b

y no

nlin

ear

regr

essi

onD

iogo

Cam

acho

, Ped

ro M

ende

s

FN36

In

ferr

ing

hum

an p

rote

in in

tera

ctio

n ne

twor

k fr

om c

onse

rvat

ivel

y hi

dden

fam

ily-f

amily

in

tera

ctio

nsF

an-K

ai L

in, C

hung

-Yen

Lin

, Cha

o A

. Hsi

ung

FN37

H

ydro

phob

ic, h

ydro

phil

ic a

nd c

harg

ed a

min

o ac

ids'

net

wor

ks w

ithi

n pr

otei

nSu

dip

Kun

du, M

d. A

ftab

uddi

n

FN38

Id

enti

fica

tion

of

mou

se h

eart

-spe

cifi

c su

bnet

wor

k st

ruct

ures

infe

rred

fro

m th

e ex

pres

sion

pr

ofile

s co

mpe

ndiu

m u

sing

a n

ew s

earc

h al

gori

thm

Seon

g-E

ui H

ong,

Seo

ng-H

wan

Rho

, Do

Han

Kim

FN39

S

truc

tura

l tra

nsit

ion

in p

roka

ryot

ic m

etab

olic

net

wor

ks w

ith

grow

th te

mpe

ratu

reK

azuh

iro

Take

mot

o, J

ose

C. N

ache

r, Ta

tsuy

a A

kuts

u

FN40

To

war

d au

tom

atic

con

stru

ctio

n of

an

evol

utio

nary

net

wor

k of

pro

tein

fam

ilie

sF

ang

fang

Xia

, Ric

k St

even

s

FN41

C

lust

erin

g of

gen

e ne

twor

ks u

sing

a M

onte

-car

lo s

imul

atio

nA

dolf

o To

rres

, Jos

e G

onza

lez,

Har

et R

osu

FN42

C

ompa

riso

n of

met

abol

ite

prod

ucti

on c

apab

ilit

y in

dice

s ge

nera

ted

by n

etw

ork

anal

ysis

m

etho

dsK

yota

Ish

ii, S

eira

Nak

amur

a, M

ineo

Mor

ohas

hi, Y

oshi

aki O

hash

i, S

hini

chi K

ikuc

hi,

Mas

ahir

o Su

gim

oto,

Mas

aru

Tom

ita

FN43

P

rote

in-p

rote

in in

tera

ctio

n pa

thw

ays

reco

nstr

ucti

on f

rom

dom

ain-

dom

ain

inte

ract

ions

Ka-

Lok

Ng,

Hsi

ang-

Chu

an L

iu, C

hien

-Hun

g H

uang

FN44

In

tegr

ated

com

puta

tion

al a

nd e

xper

imen

tal a

ppro

ach

to id

enti

y th

e ta

rget

s of

P63

on

geno

me

scal

eM

ukes

h B

ansa

l, G

iusy

Del

la G

atta

, Alb

erto

Am

besi

, Die

go d

i Ber

nard

o

FN45

G

enes

and

fun

ctio

ns th

at r

egul

ate

redo

x st

atus

in a

pho

tosy

nthe

tic

orga

nism

Raj

eev

Aur

ora,

Ran

gesh

Kun

nava

kkam

, Abh

ay K

. Sin

gh,

Mai

tray

ee B

hatt

acha

rya-

Pak

rasi

, Him

adri

B. P

akra

si

FN46

A

sys

tem

s bi

olog

y ap

proa

ch to

und

erst

and

the

regu

lato

ry n

etw

ork

gove

rnin

g tr

ansc

ript

ion

of v

irul

ence

det

erm

inan

ts in

Sta

phyl

ococ

cus

aure

usE

rik

Gus

tafs

son,

Ste

fan

Kar

lsso

n, J

an O

scar

sson

, Pet

er S

ogar

d, P

atri

c N

ilss

on, S

taff

an

Arv

idso

n

FN47

S

yste

ms

evol

utio

nary

bio

logy

: mod

ular

evo

luti

on o

f ye

ast p

rote

in in

tera

ctio

n ne

twor

kSo

ichi

Ogi

shim

a, Y

asuh

iro

Suzu

ki, T

akes

hi H

ase,

So

Nak

agaw

a, H

iros

hi T

anak

a

FN48

S

earc

h fo

r ca

usat

ive

func

tion

al S

NP

s us

ing

in v

itro

vir

us m

etho

dH

itom

i Um

eki,

Shi

geo

Fuj

imor

i, N

aohi

ro Y

anag

isaw

a, T

akan

ori W

ashi

o,

Ets

uko

Miy

amot

o-Sa

to, M

asar

u To

mit

a, H

iros

hi Y

anag

awa

FN49

To

war

d a

com

preh

ensi

ves

anal

ysis

of

hum

an tr

ansc

ript

ion

fact

or n

etw

orks

usi

ng I

VV

Ets

uko

Miy

amot

o-Sa

to, M

asam

ichi

Ish

izak

a, S

hige

o F

ujim

ori,

Rin

taro

Sai

to,

Taka

nori

Was

hio,

Nao

ya H

irai

, Kaz

uyo

Mas

uoka

, Tat

suhi

ro Y

amas

hita

, Tom

ohir

o O

shik

ubo,

Hir

oshi

Yan

agaw

a

FN50

In

ferr

ing

prot

ein

netw

ork

by m

ulti

ple

dom

ain

inte

ract

ions

Yong

Wan

g, X

iang

-Sun

Zha

ng, L

uona

n C

hen

FN51

N

oise

indu

ced

robu

st c

olle

ctiv

e be

havi

ors

in a

mul

tice

llul

ar s

yste

mR

uiqi

Wan

g, L

uona

n C

hen,

Kaz

uyuk

i Aih

ara

Com

plex

Sys

tem

s B

iolo

gy

FX01

P

heno

men

olog

ical

mod

elin

g an

d st

udy

for

the

stab

ilit

y of

a m

icro

bial

com

mun

ity

Mas

ashi

Tac

hika

wa

FX02

G

enom

e-w

ide

anal

ysis

of

cell

cyc

le d

epen

dent

gen

e ex

pres

sion

Yoic

hi M

inam

i, Ta

keya

Kas

ukaw

a, K

enic

hiro

Uno

, Tam

ami H

irai

, Hir

oki R

. Ued

a

FX03

P

lank

ton

bloo

min

gA

ndre

i Kor

obei

niko

v, S

erge

i Pet

rovs

kii

FX04

M

odel

red

ucti

on f

or v

ario

us le

vels

of

mod

el d

evel

opm

ent

Gun

nar

Ced

ersu

nd, H

enni

ng S

chm

idt,

Mat

s Ji

rstr

and

FX05

R

egul

atio

n of

E.c

oli r

espi

rati

on: g

ene

netw

ork

reco

nstr

ucti

on a

nd m

athe

mat

ical

mod

elin

gA

lexa

nder

Rat

ushn

y, T

amar

a K

hleb

odar

ova,

Vit

aly

Lik

hosh

vai

FX06

A

mul

ti-o

mic

s an

alys

is o

f E

sche

rich

ia c

oli m

etab

olic

net

wor

kM

arti

n R

ober

t, K

enji

Nak

ahig

ashi

, Nob

uyos

hi I

shii

, Tom

oya

Bab

a, T

omoy

oshi

Sog

a,

Aki

o K

anai

, Tak

ashi

Tog

ashi

, Tak

ashi

Hir

asaw

a, M

iki N

aba,

Ken

ta H

irai

, Am

inul

Hoq

ue,

Yuji

Kak

azu,

Kao

ri S

ugaw

ara,

Sao

ri I

gara

shi,

Sato

shi H

arad

a, T

akes

hi M

asud

a,

Nao

yuki

Sug

iyam

a, K

atsu

yuki

Yug

i, K

azuh

aru

Ara

kaw

a, N

ayut

a Iw

ata,

Yos

hihi

ro T

oya,

Yo

ichi

Nak

ayam

a, A

kiko

Hag

iya,

Tak

aaki

Nis

hiok

a, K

azuy

uki S

him

izu,

Hir

otad

a M

ori,

Mas

aru

Tom

ita

FX07

M

icro

tubu

le d

ynam

ics

regu

late

spi

ndle

pol

e os

cill

atio

ns a

nd p

oste

rior

dis

plac

emen

t du

ring

ana

phas

e in

the

C.e

lega

ns e

mbr

yoC

leop

atra

Koz

low

ski,

Mar

tin

Sray

ko, F

ranc

ois

Ned

elec

FX08

A

top-

dow

n m

odel

ling

app

roac

h fo

r pl

ant s

yste

ms

biol

ogy

Ada

oha

E. C

. Ihe

kwab

a, D

ougl

as B

. Kel

l, Pe

dro

Men

des

FX09

A

naly

sis

of m

utat

ion

freq

uenc

y in

ant

ibod

y af

fini

ty m

atur

atio

n: a

hin

t at p

osit

ivel

y an

d ne

gativ

ely

sele

cted

mut

atio

nsL

ei Z

hang

, Arm

in A

. Wei

ser,

Ati

jeh

Vala

i, M

icha

l Or-

Gui

l

FX10

In

sil

ico

mod

elli

ng o

f em

bryo

nic

mor

phog

enes

isP

hili

ppe-

Ale

xand

re P

ouil

le, E

mm

anue

l Bea

urep

aire

, Em

man

uel F

arge

FX11

N

on-s

uper

vise

d ph

enot

ype

lear

ning

and

phe

noty

pe m

odel

rec

onst

ruct

ion

in th

e fu

ncti

onal

ge

nom

ic s

cree

ning

s: c

oord

inat

ed a

ctiv

ity

of e

arly

end

osom

e m

otor

sYa

nnis

Kal

aidz

idis

, Joc

hen

Rin

k, M

arin

o Z

eria

l

FX12

IL

3-In

duce

d JA

K-S

TAT

sig

nali

ng: a

com

plex

sys

tem

s bi

olog

y ap

proa

chR

adin

a P.

Soe

biya

nto,

Jay

ant A

vva,

Che

ng-K

ui Q

u, K

evin

D. B

unti

ng, K

enne

th A

. Lop

aro,

M

ihaj

lo M

esar

ovic

, Sre

e N

. Sre

enat

h

43

FX13

N

FkB

and

PI3

K/A

kt p

athw

ay in

pro

stat

e ca

ncer

Jaya

nt A

vva,

Mic

hael

Wei

s, R

adin

a P.

Soe

biya

nto,

Ken

neth

A. L

opar

o, S

anja

y G

upta

, Sr

ee N

. Sre

enat

h

FX14

D

ynam

ic b

ehav

ior

of b

uffe

red

calc

ium

ions

in s

toch

asti

c an

d de

term

inis

tic

sim

ulat

ions

Juer

gen

Pah

le, S

ven

Sahl

e, U

rsul

a K

umm

er

FX16

T

he g

enet

ic c

ode

is n

earl

y op

tim

al f

or a

llow

ing

arbi

trar

y ad

diti

onal

cod

es w

ithi

n pr

otei

n-co

ding

seq

uenc

esSh

alev

Itz

kovi

tz, U

ri A

lon

FX17

G

raph

ical

cau

sal r

easo

ning

tool

for

sys

tem

s bi

olog

y: C

MA

PG

abri

el W

einr

eb, K

en J

acob

son,

Tim

othy

Els

ton

FX18

E

nzym

e I

of th

e P

EP

-dep

ende

nt p

hosp

hotr

ansf

eras

e sy

stem

: mat

hem

atic

al m

odel

ing

appr

oach

Taty

ana

Kar

elin

a, O

leg

Dem

in

FX19

S

yste

mat

ic d

eter

min

atio

n of

bio

logi

cal n

etw

ork

topo

logy

: non

-int

egra

l con

nect

ivit

y m

etho

d (N

ICM

)K

umar

Sel

vara

joo,

Mas

a Ts

uchi

ya

FX20

B

ond

grap

hs o

f ne

twor

k th

erm

odyn

amic

s ca

n ex

pres

s ph

enom

enol

ogic

al e

quat

ions

in

biol

ogic

al s

yste

ms

Yusu

ke I

mai

FX21

G

enom

e-w

ide

syst

em id

enti

fica

tion

and

ana

lysi

s re

veal

s st

able

yet

flex

ible

net

wor

k dy

nam

ics

in y

east

Mik

a G

usta

fsso

n, M

icha

el H

ornq

uist

, Joh

an B

jork

egre

n, J

espe

r Te

gner

FX22

M

odel

ing

Hsp

70-m

edia

ted

prot

ein

fold

ing

Bin

Hu,

Mat

thia

s P.

May

er, M

asar

u To

mit

a

FX23

A

spe

ctra

l app

roac

h fo

r a

prio

ri in

tegr

atio

n of

gen

e ne

twor

k kn

owle

dge

into

mic

roar

ray

clas

sifi

cati

on.

Fra

nck

Rap

apor

t, A

ndre

i Zin

ovye

v, E

mm

anue

l Bar

illo

t, J

ean-

Phi

lipp

e V

ert

FX24

R

ule-

base

d m

odel

ing

of b

ioch

emic

al n

etw

orks

bas

ed o

n pr

otei

n in

tera

ctio

ns: t

heor

y,

soft

war

e, a

nd a

ppli

cati

ons

Jam

es R

. Fae

der,

Mic

hael

L. B

lino

v, J

in Y

ang,

Byr

on G

olds

tein

, Wil

liam

S. H

lava

cek

FX25

Fa

ctor

ing

gluc

okin

ase

sequ

estr

atio

n in

sil

ico

affe

cts

glyc

olyt

ic n

etw

ork

kine

tics

Saty

a N

anda

Vel

Arj

unan

, Kum

ar S

elva

rajo

o

FX26

S

ingl

e-ce

ll a

naly

sis

and

mod

elin

g re

veal

that

HIV

& H

erpe

s us

e fe

edba

ck c

ircu

its

to

cont

rol l

ifec

ycle

Leo

r W

einb

erge

r, T

hom

as S

henk

FX27

C

haot

ic th

erm

oreg

ulat

ion

in th

e sp

adix

of

skun

k ca

bbag

e, S

ympl

ocar

pus

foet

idus

Taka

nori

Ito

, Hir

oshi

Osa

da, K

ikuk

atsu

Ito

FX28

A

djoi

nt b

ased

par

amet

er id

enti

fica

tion

alg

orit

hm f

or p

rote

in n

etw

orks

wit

h ap

plic

atio

n to

pl

anar

cel

l pol

arit

yR

obin

L. R

affa

rd, C

lair

e J.

Tom

lin,

Kei

th A

mon

lird

vim

an, J

effr

ey D

. Axe

lrod

FX29

S

elec

tion

of

opti

mal

gro

wth

sta

te b

y st

ocha

stic

noi

seC

hika

ra F

urus

awa,

Kun

ihik

o K

anek

o

FX30

“S

yste

ms

ener

geti

cs”

-a n

ew a

ppro

ach

for

cell

ular

sys

tem

s dy

nam

ics

Nor

iko

Hir

oi, A

kira

Fun

ahas

hi, H

iroa

ki S

uzuk

i, T

akat

oki Y

amam

oto,

Dou

glas

Mur

ray

FX31

C

hara

cter

izat

ion

of p

rote

ins

from

the

mat

rix

of s

cler

ites

fro

m th

e al

cyon

aria

n,

Lob

ophy

tum

cra

ssum

.M

. Azi

zur

Rah

man

, Yei

shin

Isa

, Tsu

yosh

i Ueh

ara

FX32

A

n at

tem

pt a

t usi

ng th

e ap

proa

ches

in s

yste

ms

biol

ogy

to e

xplo

re tr

adit

iona

l Chi

nese

m

edic

ine

Chu

-shi

ang

Che

n, S

heng

-Yin

g Pa

o, S

ong-

shia

ng L

in, K

athe

rine

Che

n

FX33

T

he b

enefi

t of

com

bini

ng s

yste

ms

biol

ogy

and

expe

rim

ents

for

und

erst

andi

ng c

ompl

ex

biol

ogic

al s

yste

ms

Mag

nus

Fag

erli

nd, E

rik

Gus

tafs

son,

Eli

e Ja

rnm

ark,

Mar

ia S

vens

son,

Pet

er S

ogar

d

FX34

Q

uant

itat

ive

biol

ogy

of e

mbr

yo-m

ater

nal c

omm

unic

atio

n an

d im

plan

tati

onSt

efan

Bau

ersa

chs,

Cla

udia

Kle

in, F

rank

Ber

endt

, Tho

mas

Fro

hlic

h, H

elm

ut B

lum

, G

eorg

J. A

rnol

d, U

lric

h M

ansm

ann,

Eck

hard

Wol

f

Con

trol

and

Sys

tem

The

ory

for

Syst

ems

Bio

logy

FT01

A

fini

te m

odel

for

the

rand

om b

ehav

ior

in th

e la

ctos

e re

gula

tion

sys

tem

of

Esc

heri

chia

co

liA

. Agu

ng J

uliu

s, A

dam

Hal

asz,

Vij

ay K

umar

, Geo

rge

J. P

appa

s

FT02

In

viv

o re

acti

on m

odel

ing

by D

RR

KN

orik

o H

iroi

, Aki

ra F

unah

ashi

, Hir

oaki

Kit

ano

FT03

M

odel

ing,

sim

ulat

ion

& s

tabi

lity

ana

lysi

s of

p53

-mdm

2 os

cill

atio

nsA

run

Kri

shna

n, M

asar

u To

mit

a

FT04

Pa

ram

eter

per

turb

atio

n an

alys

is o

f ba

cter

ial c

hem

otax

isTa

e-H

wan

Kim

, Sun

g H

oon

Jung

, Kw

ang-

Hyu

n C

ho

FT05

E

xper

imen

t des

ign

for

para

met

er e

stim

atio

n in

mod

els

com

bini

ng s

igna

l tra

nsdu

ctio

n an

d m

etab

olic

pat

hway

s: c

ontr

ol o

f ni

trog

en u

ptak

e in

yea

stN

atal

A. W

. Van

Rie

l

FT06

P

ropo

rtio

n pr

eser

vati

on in

a g

row

ing

tiss

ueA

kihi

ko N

akaj

ima,

Kun

ihik

o K

anek

o

FT07

E

xper

imen

t des

ign

for

opti

mal

exc

itat

ion

of g

ene

regu

lato

ry n

etw

orks

Torb

joer

n E

. M. N

ordl

ing,

Ell

ing

W. J

acob

sen

FT08

E

volu

tion

ary

desi

gn p

rinc

iple

s of

bac

teri

al c

hem

otax

isM

arku

s K

ollm

ann,

Lin

da L

ovdo

k, K

ilia

n B

arth

olom

e, J

ens

Tim

mer

, Vic

tor

Sour

jik

FT09

E

nsem

ble

mod

elli

ng r

evea

ls a

nov

el lo

gic

of T

OR

sig

nall

ing

in y

east

Lar

s K

uepf

er, M

atth

ias

Pet

er, U

we

Saue

r, J

oerg

Ste

llin

g

FT10

S

yste

ms

biol

ogy

of b

one

rem

odel

ing

in o

steo

poro

sis

Kal

yan

Myn

ampa

ti, W

en W

an L

ing,

Pet

er L

ee

44

FT11

Fr

om b

urst

s to

mol

ecul

ar m

emor

y: fi

ndin

g th

e fu

ndam

enta

l uni

ts o

f bi

oche

mic

al

fluc

tuat

ions

Juan

M. P

edra

za, J

ohan

Pau

lsso

n

FT12

Ta

ckli

ng th

e un

cert

aint

y of

tum

our

dyna

mic

sA

bhik

Muk

herj

ee, D

urjo

y M

ajum

der,

Sur

yasa

rath

i Bar

at

FT14

R

obus

t ide

ntifi

cati

on o

f bi

oche

mic

al n

etw

orks

fro

m n

oisy

mea

sure

men

tsJo

ngra

e K

im, D

ecla

n G

. Bat

es, I

an P

ostl

ethw

aite

, Pat

Hes

lop-

Har

riso

n,

Kw

ang-

Hyu

n C

ho

FT15

C

ello

gica

: a to

ol to

ana

lyze

and

con

trol

the

dyna

mic

s of

cis

-reg

ulat

ory

syst

ems

Saty

a N

anda

Vel

Arj

unan

, Zhe

n X

uan

Yeo,

Mas

aru

Tom

ita,

Mas

a T

such

iya

FT16

A

naly

zing

rob

ustn

ess

in b

ioph

ysic

al n

etw

orks

: app

lica

tion

to a

popt

osis

Jaso

n E

. Sho

emak

er, F

ranc

is J

. Doy

le I

II

FT17

E

xper

imen

tal d

esig

n an

d m

odel

sel

ecti

on f

or s

igna

l tra

nsdu

ctio

n pa

thw

ays

Tho

mas

Mai

wal

d, C

lem

ens

Kre

utz,

Seb

asti

an B

ohl,

Mar

cel S

chil

ling

, Urs

ula

Kli

ngm

uell

er,

Jens

Tim

mer

FT18

A

MD

E p

ersp

ectiv

e on

cod

ing

of s

yste

ms

biol

ogy:

pro

of o

f co

ncep

t usi

ng tr

ansf

orm

atio

ns

to B

ioA

mbi

ents

and

ana

lysi

sD

ebor

a Sc

huch

da

Ros

a, M

agal

i Rou

x-R

ouqu

ie, M

arie

-Noe

lle

Terr

asse

, Cor

rado

Pri

ami

FT19

B

iolo

gica

l reg

ulat

ions

as

fini

te m

arko

v pr

oces

sR

eiko

J. T

anak

a, H

iden

ori K

imur

a, H

iroy

uki O

kano

FT20

G

enom

e si

ze e

stim

ates

and

kar

yoty

pes

for

thre

e im

port

ant f

resh

wat

er m

ollu

scs,

the

Lym

naea

nat

alen

sis

and

the

schi

stos

omia

sis

vect

or s

nail

s ( B

iom

phal

aria

ale

xand

rina

and

B

ulin

us tr

unca

tus)

Fay

ez A

. Bak

ry, A

hmed

T. S

hara

f El-

Din

FT21

T

Sim

, a p

latf

orm

for

sim

ulat

ion

of m

ulti

-cel

lula

r sy

stem

sA

rios

to S

ique

ira

Silv

a, J

ose

And

res Y

unes

FT22

D

ynam

ics

of H

IV in

fect

ion

stud

ied

wit

h C

onfo

rmon

-P s

yste

ms

Dav

id W

. Cor

ne, P

ierl

uigi

Fri

sco

FT23

A

sys

tem

atic

mod

elin

g fr

amew

ork

for

bioc

hem

ical

and

bio

logi

cal s

yste

ms

Hen

ning

Sch

mid

t, M

ats

Jirs

tran

d, G

unna

r C

eder

sund

FT24

Pa

ram

eter

est

imat

ion

usin

g al

tern

ativ

e co

st f

unct

ions

Hen

ning

Sch

mid

t, G

unna

r C

eder

sund

, Mat

s Ji

rstr

and

FT26

M

omen

t clo

sure

app

roxi

mat

ions

for

stu

dyin

g st

ocha

stic

ity

in b

iolo

gica

l sys

tem

sA

bhyu

dai S

ingh

, Joa

o Pe

dro

Hes

panh

a

FT27

U

nrav

elin

g fe

edba

ck s

truc

ture

s in

gen

e re

gula

tory

net

wor

ks w

ith

appl

icat

ion

to th

e m

amm

alia

n ci

rcad

ian

cloc

kC

amil

la T

rane

, Ell

ing

W. J

acob

sen

Synt

heti

c B

iolo

gy

FS01

Te

stin

g bi

olog

ical

erg

odic

ity

of to

ggle

sw

itch

and

rec

onst

ruct

ion

of s

ingl

e-ce

ll-b

ehav

ior

from

pop

ulat

ion-

leve

l-m

easu

rem

ent

Hir

okaz

u To

zaki

, Tet

suya

J. K

obay

ashi

, Hir

oyuk

i Oka

no, R

yo Y

amam

oto,

Kaz

uyuk

i Aih

ara,

H

iden

ori K

imur

a

FS02

S

topp

ing

mam

mal

ian

circ

adia

n cl

ock

by c

riti

cal l

ight

pul

se: d

eath

of

indi

vidu

al o

scil

lato

rs

or d

esyn

chro

niza

tion

of

osci

llat

ors?

Tets

uya

J. K

obay

ashi

, Hid

eki U

kai,

Hir

oki R

. Ued

a

FS03

C

onst

ruct

ion

and

perf

orm

ance

cha

ract

eris

tics

of

a se

lf-g

ener

atin

g in

vit

ro m

etab

olic

re

acti

onN

ancy

Kel

ley-

Lou

ghna

ne, M

auri

cio

Rod

rigu

ez, M

arli

n L

inge

r, L

atha

Nar

ayan

an,

John

Fra

zier

FS05

P

rogr

amm

able

bac

teri

al c

atal

ysts

Mig

uel G

odin

ho d

e A

lmei

da, J

acek

Puc

halk

a, A

mit

Kha

chan

e, K

enne

th T

imm

is,

Vit

or M

arti

ns d

os S

anto

s

FS06

R

egul

ator

y dy

nam

ics

of s

ynth

etic

gen

e ne

twor

ks w

ith

posi

tive

feed

back

Yusu

ke T

. Mae

da, M

asak

i San

o

FS07

D

e no

vo c

onst

ruct

ion

of g

ene

regu

lati

on n

etw

ork

in s

mal

l ves

icle

Dai

suke

Kig

a, M

asah

iro

Taki

noue

, Koh

-ich

iroh

Sho

hda,

Aki

ra S

uyam

a

FS08

In

sil

ico

geno

me-

scal

e an

alys

is o

f th

e hy

pert

herm

ophi

lic

bact

eriu

m, T

herm

otog

a ne

apol

itan

aJi

n Si

k K

im, J

ae J

ong

Kim

, Ki J

ung

Par

k, S

ang

Yup

Lee

FS09

E

ngin

eeri

ng s

ynth

etic

tran

s-sp

lici

ng r

iboz

yme

syst

ems

Aus

tin

Che

FS10

Po

pula

tion

ana

lysi

s of

lipo

som

es w

ith

prot

ein

synt

hesi

s an

d a

casc

adin

g ge

neti

c ne

twor

kTa

kesh

i Sun

ami,

Kan

etom

o Sa

to, K

eita

ro I

shik

awa,

Tet

suya

Yom

o

Nov

el C

ompu

tati

onal

Env

iron

men

ts f

or S

yste

ms

Bio

logy

FI01

S

BM

L le

vel 2

ver

sion

2A

ndre

w F

inne

y, M

icha

el H

ucka

, Nic

olas

Le

Nov

ere

FI02

T

he S

BM

L la

yout

ext

ensi

on a

nd b

eyon

dR

alph

Gau

ges,

Sve

n Sa

hle,

Urs

ula

Ros

t, K

atja

Weg

ner

FI03

T

he s

yste

ms

biol

ogy

onto

logy

Mel

anie

Cou

rtot

, Mic

hael

Huc

ka, N

icol

as L

e N

over

e

FI04

M

IRIA

M d

atab

ase

and

web

serv

ices

Cam

ille

Lai

be, M

elan

ie C

ourt

ot, M

arco

Don

izel

li, C

hen

Li,

Nic

olas

Le

Nov

ere

FI05

B

ioM

odel

s da

taba

se, a

cur

ated

res

ourc

e of

ann

otat

ed p

ubli

shed

mod

els

Che

n L

i, M

arco

Don

izel

li, L

u L

i, H

aris

h D

haru

ry, A

rnau

d H

enry

, Mic

hael

Huc

ka,

Nic

olas

Le

Nov

ere

45

FI06

R

ecen

t upd

ates

to li

bSB

ML

, Mat

hSB

ML

, SB

MLT

oolb

ox, a

nd th

e S

BM

L.o

rg o

nlin

e va

lida

tor

Ben

jam

in B

orns

tein

, Sar

ah M

. Kea

ting

, Bru

ce S

hapi

ro, J

oann

a M

urak

ami,

Mic

hael

H

ucka

FI07

S

BM

Led

itor

: an

edit

or f

or m

odel

s in

the

syst

ems

biol

ogy

mar

kup

lang

uage

Nic

olas

Rod

rigu

ez, N

icol

as L

e N

over

e, M

arco

Don

izel

li

FI08

C

ellD

esig

ner3

.1: a

pro

cess

dia

gram

edi

tor

for

gene

-reg

ulat

ory

and

bioc

hem

ical

net

wor

ksA

kira

Fun

ahas

hi, A

kiya

Jou

raku

, Yuk

iko

Mat

suok

a, N

orih

iro

Kik

uchi

, Hir

oaki

Kit

ano

FI09

In

tegr

atin

g to

ols

for

com

puta

tion

al s

yste

ms

biol

ogy:

PyS

CeS

and

JW

S o

nlin

eB

rett

G. O

livi

er, J

ohan

n M

. Roh

wer

, Jac

ky L

. Sno

ep, J

an-H

endr

ik S

. Hof

mey

r

FI10

Ta

vern

a w

orkfl

ows

for

syst

ems

biol

ogy

Pet

er L

i, A

ndy

Bra

ss, J

ohn

Pin

ney,

Tom

Oin

n, D

ougl

as K

ell,

Car

ole

Gob

le

FI11

C

OPA

SI

- a

com

plex

pat

hway

sim

ulat

orSv

en S

ahle

, Ste

fan

Hoo

ps, R

alph

Gau

ges,

Jue

rgen

Pah

le, P

edro

Men

des,

Urs

ula

Kum

mer

FI12

S

yste

ms

biol

ogy

soft

war

e su

ppor

t in

mat

hem

atic

a: r

ecen

t dev

elop

men

ts in

cel

lera

tor

Bru

ce E

. Sha

piro

, Ale

xey

Voro

byov

, Joa

nna

G. M

urak

ami,

Eri

c D

. Mjo

lsne

ss

FI13

S

IBio

Net

: SB

ML

app

lica

tion

for

sys

tem

iden

tifi

cati

on o

f bi

oche

mic

al r

eact

ion

netw

orks

Ats

ushi

Shi

nkai

, Jun

ichi

ro Y

oshi

mot

o, K

enji

Doy

a

FI14

D

ynaB

ioS

.Cel

l: a

new

gen

eral

sim

ulat

or f

or c

ell p

hysi

olog

ical

mod

els

to f

acil

itat

e si

mul

atio

n of

exp

erim

enta

l pro

toco

lsTa

kao

Shim

ayos

hi, A

kira

Am

ano,

Tet

suya

Mat

suda

FI15

C

AD

LIV

E: c

ompu

ter-

aide

d de

sign

of

livin

g sy

stem

sK

enta

rou

Inou

e, H

iroy

uki K

urat

a

FI16

C

ompr

ehen

sive

stu

dy o

f nu

mer

ical

sol

vers

in c

ompl

ex o

scil

lato

ry b

ioch

emic

al s

yste

ms

mod

elin

gM

ay W

ang,

Cha

ng F

Quo

FI17

A

tool

for

ana

lysi

s in

"dy

nam

ical

cha

nge

beha

vior

ove

r m

otif

s"Ji

ttis

ak S

enac

hak,

Tom

oyuk

i Yam

amot

o, K

okic

hi F

utat

sugi

FI18

F

ly-D

PI:

dat

abas

e of

pro

tein

inte

ract

omes

for

D. m

elan

ogas

ter

in th

e ap

proa

ch o

f sy

stem

s bi

olog

yC

hung

-Yen

Lin

, Chi

-Shi

ang

Cho

, Chi

a-L

ing

Che

n, F

an-K

ai L

in, C

hieh

-Hua

Lin

, P

ao-Y

ang

Che

n, S

hu-H

wa

Che

n, C

hen-

Zen

Lo,

Cha

o A

. Hsi

ung

FI19

D

atab

ase

driv

en a

ppro

ach

for

auto

mat

ic c

onst

ruct

ion

of d

ynam

ic c

ell-

wid

e m

etab

olic

pa

thw

ay m

odel

sK

azuh

aru

Ara

kaw

a, Y

ukin

o O

gaw

a, M

asar

u To

mit

a

FI20

V

isua

liza

tion

of

Cel

lML

mod

els

Sara

la D

issa

naya

ke, M

att H

alst

ead,

Pou

l Nie

lsen

FI21

A

gra

phic

al n

otat

ion

to d

escr

ibe

the

logi

cal i

nter

acti

ons

of b

iolo

gica

l pat

hway

sSt

uart

L. M

oodi

e, A

nato

ly S

orok

in, I

gor

Gor

yani

n, P

eter

Gha

zal

FI22

G

oogl

ing

cred

ible

inte

ract

ions

fro

m p

rote

in-p

rote

in in

tera

ctio

n ne

twor

ksK

inya

Oka

da, M

asan

ori A

rita

, Kiy

oshi

Asa

i

FI23

A

n in

tegr

ativ

e da

taba

se f

or b

ioch

emic

al r

eact

ion

kine

tics

: SA

BIO

-RK

Ren

ate

Kan

ia, U

lrik

e W

itti

g, M

arti

n G

oleb

iew

ski,

And

reas

Wei

dem

ann,

Olg

a K

rebs

, Sa

qib

Mir

, Isa

bel R

ojas

FI24

In

tegr

atio

n of

gen

e ex

pres

sion

dat

a w

ith

bio-

mol

ecul

ar in

tera

ctio

n ne

twor

ks b

y us

ing

repo

rter

fea

ture

s al

gori

thm

Ana

Pau

la O

live

ira,

Kir

an R

aosa

heb

Pati

l, Je

ns N

iels

en

FI25

U

sing

var

iabl

e se

lect

ion

met

hod

to in

fer

gene

reg

ulat

ory

netw

orks

fro

m ti

me

seri

es

mic

roar

ray

data

Dou

gu N

am, C

heol

-Gu

Hur

, Jih

yun

F. K

im

FI26

To

war

ds a

sig

nal t

rans

duct

ion

netw

ork

of y

east

Kut

lu O

. Ulg

en, K

. Yal

cin

Arg

a, Z

. Ils

en O

nsan

, Bet

ul K

irda

r, Je

ns N

iels

en

FI27

C

ompu

ter-

base

d sc

reen

ing

of f

unct

iona

l con

form

ers

of p

rote

ins

Hec

tor

M M

onti

el M

olin

a, G

abri

el D

el R

io

FI28

A

n in

fras

truc

ture

to c

onst

ruct

gen

ome-

scal

e m

etab

olic

mod

els

auto

mat

ical

lyX

ingh

ua S

hi, R

ick

Stev

ens

FI29

T

RN

Dy:

a b

ioin

form

atic

s to

ol f

or in

vest

igat

ing

the

topo

logi

cal d

ynam

ics

of d

iffe

rent

ially

ex

pres

sed

gene

s in

tran

scri

ptio

nal r

egul

ator

y ne

twor

ksD

uang

dao

Wic

hada

kul,

Ram

Sam

udra

la

FI30

P

rote

in n

etw

ork

cons

truc

tion

of

Can

dida

alb

ican

s fr

om S

acch

arom

yces

cer

evis

iae’

s pr

otei

n-pr

otei

n in

tera

ctio

nsC

hieh

-Hua

Lin

, Chu

ng-Y

en L

in, F

an-K

ai L

in, C

hi-S

hian

g C

ho, C

hia-

Lin

g C

hen,

P

ao-Y

ang

Che

n, C

hen-

Zen

Lo,

Cha

o A

. Hsi

ung

FI31

In

tera

ctiv

e vi

sual

izat

ion

of c

ompl

ex a

nd s

truc

ture

d bi

olog

ical

net

wor

ksSe

bast

ian

Mir

sche

l, M

arti

n G

inke

l, J

ulio

Sae

z-R

odri

guez

, Ern

st D

iete

r G

ille

s

FI32

K

inet

ikon

HT,

a d

atab

ase

of k

inet

ic p

aram

eter

s, c

reat

ed u

sing

hig

h th

roug

hput

tech

niqu

es.

Axe

l Kow

ald,

Seb

asti

an S

chm

eier

, Mar

vin

Schu

lz, W

olfr

am L

iebe

rmei

ster

, Si

mon

Bor

ger,

Edd

a K

lipp

FI33

Po

tter

sWhe

el: u

ser-

frie

ndly

hig

h-pe

rfor

man

ce p

aram

eter

est

imat

ion

& m

odel

sel

ecti

on

Mat

lab

fram

ewor

kT

hom

as M

aiw

ald,

Cle

men

s K

reut

z, J

ens

Tim

mer

FI34

S

yste

ms

biol

ogy

anal

ysis

of

endo

cyto

sis

and

sign

alli

ng in

mam

mal

ian

cell

sM

arin

o Z

eria

l, J

oche

n R

ink,

Cla

udio

Col

line

t, C

harl

es B

rads

haw

, Bia

nca

Hab

erm

ann,

Ya

nnis

Kal

aidz

idis

, Per

la D

el C

onte

-Zer

ial,

Lut

z B

rusc

h, A

ndre

as D

euts

ch

FI35

T

herm

odyn

amic

al m

odel

of

DN

A h

ybri

diza

tion

on

shor

t oli

gonu

cleo

tide

mic

roar

ray

Nao

aki O

no, S

hing

o Su

zuki

, Chi

kara

Fur

usaw

a, A

kiko

Kas

hiw

agi,

Tet

suya

Yom

o

FI36

P

redi

ctin

g de

lete

riou

s S

NP

s w

ith

site

-spe

cifi

c ev

olut

iona

ry m

odel

sA

nna

A. C

hern

ova,

Ben

jam

in P

. Bla

ckbu

rne,

Ric

hard

A. G

olds

tein

FI37

E

valu

atin

g th

e fu

ncti

onal

coh

eren

ce o

f pr

otei

n gr

oups

via

pro

tein

-sem

anti

c ne

twor

kB

in Z

heng

, Xin

ghua

Lu

46

FI38

Fr

om in

sil

ico

QT

Ls

to s

yste

m b

iolo

gy: a

n ex

ampl

e of

usi

ng in

sil

ico

map

ping

to id

enti

fy

gene

tic

cont

ribu

tion

to v

aria

tion

of

bono

mas

s de

nsit

y in

inbr

ed s

trai

nsP

aul L

. F. T

ang,

Mat

thew

S. Y

. Cha

n, P

ak C

. Sha

m, Y

ou-q

iang

Son

g

FI39

N

umer

ical

sim

ulat

ion

and

mol

ecul

ar s

yste

ms

biol

ogy

Koi

chi T

akah

ashi

FI40

Pa

ram

eter

est

imat

ion

for

stif

f eq

uati

ons

of b

iosy

stem

s us

ing

radi

al b

asis

fun

ctio

n ne

twor

ksYo

shiy

a M

atsu

bara

, Shi

nich

i Kik

uchi

, Mas

ahir

o Su

gim

oto,

Mas

aru

Tom

ita

FI41

B

ioU

ML

− o

pen

sour

ce e

xten

sibl

e w

orkb

ench

for

sys

tem

s bi

olog

yFe

dor

A. K

olpa

kov,

Mik

hail

V. P

uzan

ov, A

lexa

nder

V. K

oshu

kov

FI42

A

uni

vers

al r

ate

equa

tion

for

com

puta

tion

al s

yste

ms

biol

ogy

Joha

nn M

. Roh

wer

, Arn

o J.

Han

ekom

, Jan

-Hen

drik

S. H

ofm

eyr

FI43

M

etaF

luxN

et2:

an

inte

grat

ed e

nvir

onm

ent f

or m

odel

ing

and

sim

ulat

ion

of g

enom

e-sc

ale

met

abol

ic n

etw

ork

mod

elH

ongs

eok

Yun,

Cho

amun

Yun

, Hyu

n U

k K

im, S

ang

Yup

Lee

FI44

S

yste

m-l

evel

iden

tifi

cati

on o

f tr

ansc

ript

iona

l cir

cuit

s un

derl

ying

dro

soph

ila

circ

adia

n cl

ocks

usi

ng d

roso

phil

a ti

ling

arr

ays

Rik

uhir

o G

. Yam

ada,

Mak

i Uka

i Tad

enum

a, K

en-i

chir

o D

. Uno

, Tak

eya

Kas

ukaw

a,

Aki

ra M

atsu

mot

o, H

irok

i R. U

eda

FI45

Id

enti

fyin

g ge

nes

wit

h si

gnifi

cant

inte

ract

ion

effe

cts

in to

xico

logi

cal t

ime-

cour

se

mic

roar

ray

data

Yan

Ma,

E. J

ames

Har

ner

FI46

D

evel

opm

ent o

f co

mpu

tati

onal

met

hods

for

ana

lysi

s of

met

abol

ite

scre

enin

g da

taP

riti

Tal

war

, Tho

mas

Len

gaue

r, C

hris

toph

Wit

tman

n, V

idya

Vel

agap

udhi

, Elm

ar H

einz

le

FI47

To

p-do

wn

appr

oach

for

dec

iphe

ring

cha

ract

eris

tics

of

met

abol

ic r

eact

ions

fro

m

expe

rim

enta

l dat

aJu

ng-W

ook

Ban

g, T

im E

bbel

s, F

lore

ncio

Paz

os

FI48

A

gen

eric

mas

s sp

ectr

omet

ry-b

ased

pla

tfor

m f

or e

nzym

e ki

netic

dat

a ac

quis

ition

and

an

alys

isR

icha

rd B

aran

, Tak

amas

a Is

hika

wa,

Nat

sum

i Sai

to, Y

uji K

akaz

u, T

omoy

oshi

Sog

a,

Taka

aki N

ishi

oka,

Mar

tin

Rob

ert,

Mas

aru

Tom

ita

FI49

R

ole

of th

e bg

l ope

ron

of E

sche

rich

ia c

oli i

n st

atio

nary

pha

seR

anjn

a M

adan

, S. M

ahad

evan

FI50

T

he M

anch

este

r ce

ntre

for

inte

grat

ive

syst

ems

biol

ogy

Dou

glas

B. K

ell,

Dav

id S

. Bro

omhe

ad, S

imon

J. G

aske

ll, J

ohn

McC

arth

y,

Step

hen

G. O

live

r, N

orm

an P

aton

, Han

s V.

Wes

terh

off

FI51

A

kin

etic

app

roac

h to

the

anal

ysis

of

non-

stea

dy s

tate

isot

ope

trac

er d

ata

Vit

aly

Seli

vano

v, S

ilvi

a M

arin

, Ant

onio

Ram

os-M

onto

ya, J

osep

Cen

tell

es, P

aul L

ee,

Mar

ta C

asca

nte

FI52

In

terp

ret l

ipid

met

abol

omic

pat

hway

dat

a us

ing

visu

aliz

atio

nG

eoff

rey

Wan

g, J

in-Y

oung

Hon

g, A

lfre

d M

erri

ll, M

ay D

. Wan

g

FI53

R

ever

se e

ngin

eeri

ng f

or e

mbr

yoni

c ge

ne r

egul

ator

y ne

twor

k in

zeb

rafi

sh v

ia e

volu

tion

ary

opti

miz

atio

n w

ith

data

col

loca

tion

Wen

-Hun

g H

unag

, Chi

ou-H

wa

Yuh,

Fen

g-Sh

eng

Wan

g

FI54

G

enom

e an

nota

tion

and

met

abol

ic n

etw

ork

cons

truc

tion

of

Asp

ergi

llus

ory

zae

Wan

wip

a V

ongs

angn

ak, P

eter

Bja

rke

Ols

en, S

teen

Kro

gsga

ard,

Jen

s N

iels

en

FI55

C

hara

cter

izat

ion

of r

egul

ator

y m

odul

es a

ssoc

iate

d w

ith

stem

cel

l dif

fere

ntia

tion

by

late

nt

vari

able

mod

els

Je-G

un J

oung

, Don

gho

Shin

, Rho

Hyu

n Se

ong,

Byo

ung-

Tak

Zha

ng

FI56

V

irtu

al m

icro

scop

y -

mod

ular

mod

elin

g of

exp

erim

enta

l pro

toco

ls a

nd in

stru

men

tati

onJa

mes

Sch

aff,

Anu

radh

a L

aksh

min

aray

ana,

Ion

Mor

aru,

Les

lie

Loe

w

FI57

H

igh-

thro

ughp

ut im

age

anal

ysis

of

subc

ellu

lar

loca

liza

tion

pat

tern

s of

fluo

resc

ently

la

bele

d pr

otei

nsF

abia

n K

ampe

r, O

laf S

elch

ow, D

imit

rios

Kal

amat

iano

s, H

aral

d W

ajan

t,

Kla

us P

fizen

mai

er, E

ric

Bul

ling

er

FI58

A

ppli

ed g

enom

e-sc

ale

mod

elli

ng o

f as

perg

illu

s ni

ger

Mik

ael R

. And

erse

n, M

icha

el L

. Nie

lsen

, Jen

s N

iels

en

FI59

Q

uali

ty c

ontr

ol a

nd im

prov

ed q

uant

itat

ive

wes

tern

blo

ttin

g w

ith

the

geli

nspe

ctor

Tho

mas

Mai

wal

d, M

arce

l Sch

illi

ng, S

ebas

tian

Boh

l, C

lem

ens

Kre

utz,

U

rsul

a K

ling

mue

ller

, Jen

s T

imm

er

FI60

In

tegr

atio

n of

bio

logi

cal p

athw

ays

Yu-T

ai W

ang,

Yei

ng-W

en D

eng,

Che

ng-M

in W

ei, U

eng-

Che

ng Y

ang

FI61

B

ayes

ian

syst

em id

enti

fica

tion

of

bioc

hem

ical

sig

nali

ng p

athw

ays

Juni

chir

o Yo

shim

oto,

Ats

ushi

Shi

nkai

, Ken

ji D

oya

FI62

In

tegr

ativ

e bi

oinf

orm

atic

s an

alys

is th

at d

econ

volu

tes

the

chan

ges

of tr

ansc

ript

iona

l re

gula

tory

pro

gram

s du

ring

car

cino

gene

sis

Ats

ushi

Nii

da, S

huic

h Ts

utsu

mi,

And

rew

Sm

ith,

Mic

hael

Q. Z

hang

, Hir

oyuk

i Abu

rata

ni,

Tets

u A

kiya

ma

FI63

G

enom

ic s

igna

ture

s fo

r dr

ug-i

nduc

ed a

popt

osis

in c

ance

r ce

ll li

nes:

a c

ombi

ned

expe

rim

enta

l and

sta

tL

aure

nt G

auti

er, C

hris

toph

er T

aylo

r, H

arol

d B

rook

s, P

hili

p Iv

erse

n, C

harl

es S

penc

er,

Xia

ng Y

ang,

Gre

g Tu

cker

-Kel

logg

FI64

O

ptim

izat

ion

of c

DN

A m

icro

arra

ys u

sing

cri

teri

a th

at d

o no

t rel

y on

ext

erna

l sta

ndar

dsTo

runn

Bru

land

, End

re A

nder

ssen

, Ber

it D

oset

h E

itre

m, H

allg

eir

Ber

gum

, V

idar

Bei

svag

, Ast

rid

Lae

grei

d

FI65

Id

enti

fica

tion

and

des

ign

of in

ter-

and

intr

a-m

olec

ular

ato

mic

net

wor

k by

usi

ng th

e ge

nom

ic s

eque

nces

and

the

stru

ctur

al in

form

atio

nYo

hei K

oyam

a, T

etsu

ya J

. Kob

ayas

hi, S

huji

Tom

oda,

Hir

oki R

. Ued

a

FI66

C

ompo

siti

on a

nd a

ggre

gati

on f

or b

iolo

gica

l pat

hway

mod

elin

gR

anji

t Ran

dhaw

a, C

liffo

rd A

. Sha

ffer,

John

J. T

yson

47

FI67

A

n ac

cele

rati

on o

f a

bioc

hem

ical

sim

ulat

or o

n pr

ogra

mm

able

har

dwar

eYo

w I

wao

ka, Y

asun

ori O

sana

, Mas

ato

Yosh

imi,

Tos

inor

i Koj

ima,

Yur

i Nis

hika

wa,

A

kira

Fun

ahas

hi, N

orik

o H

iroi

, Yui

chir

o Sh

ibat

a, N

aoki

Iw

anag

a, H

iroa

ki K

itan

o,

Hid

ehar

u A

man

o

FI68

Fi

D -

a to

ol f

or p

redi

ctio

n of

mol

ecul

ar f

ragm

ents

fro

m ta

ndem

mas

s sp

ectr

omet

ry d

ata

Mar

kus

Hei

none

n, A

ri R

anta

nen,

Tan

eli M

ieli

kain

en, E

sa P

itka

nen,

Juh

o R

ousu

FI69

C

ompa

rativ

e ‘O

mic

s’ a

naly

sis

of E

sche

rich

ia c

oli B

and

K-1

2Su

ng H

o Yo

on, H

aeyo

ung

Jeon

g, C

heol

-Goo

Hur

, Tae

Kw

ang

Oh,

Jih

yun

F. K

im

FI70

S

yste

ms

biol

ogy

grap

hica

l not

atio

n (S

BG

N)

proj

ect

Hir

oaki

Kit

ano,

Mic

hael

Huc

ka, N

icol

as L

e N

over

e, A

kira

Fun

ahas

hi

FI71

P

redi

ctin

g an

tige

nic

drif

t in

hum

an in

flue

nza

A v

irus

H3

hem

aggl

utin

inYu

-Chi

eh L

iao,

Chi

n-Yu

Ko,

Min

-Shi

Lee

, Cha

o A

. Hsi

ung

FI72

W

ebC

ell:

a w

eb-b

ased

inte

grat

ed e

nvir

onm

ent f

or m

anag

ing

and

anal

yzin

g ce

llul

ar

netw

ork

mod

els

Cho

amun

Yun

, Don

g-Yu

p L

ee, A

youn

Cho

, Sun

won

Par

k, S

ang

Yup

Lee

FI73

L

inea

r an

d co

nfor

mat

iona

l epi

tope

s pr

edic

tion

fro

m m

embe

r of

pro

tein

fam

ilie

sTu

n-W

en P

ai, W

ei-J

un Z

hung

, Chi

h-H

ong

Liu

, Wen

-Shy

ong

Tzou

FI74

Id

enti

fica

tion

of

hete

roge

neou

s na

med

ent

itie

s in

bio

logy

text

s an

d re

solu

tion

of

anap

hora

Juli

en L

orec

, Ger

ard

Ram

stei

n, Y

anni

ck J

acqu

es

FI75

B

ioC

AD

: web

ser

vice

bas

ed in

tegr

ated

sys

tem

for

infe

rrin

g ge

neti

c re

gula

tory

cir

cuit

sSa

ngw

oo K

im, K

iryo

ng H

a, D

oheo

n L

ee

FI76

In

tegr

atin

g m

icro

arra

y da

ta a

naly

sis

and

prot

ein-

prot

ein

inte

ract

ion

data

base

to c

onst

ruct

dy

nam

ic b

iolo

gica

l net

wor

ks w

hich

rep

rese

nt th

e ch

arac

teri

stic

s of

gen

e ex

pres

sion

pa

tter

nP

eter

Kua

n-Ye

u P

an, C

hen-

Hsi

ung

Cha

n, S

heng

-An

Lee

, Che

ng-Y

an K

au, I

-Min

g C

hu

FI77

A

vie

w to

the

evol

utio

n of

bio

logi

cal p

athw

ays

usin

g PA

NT

HE

R.

Hua

iyu

Mi,

Nan

Guo

, Ani

sh K

ejar

iwal

, Pau

l Tho

mas

FI78

S

BW

− a

mod

ular

fra

mew

ork

for

Sys

tem

s B

iolo

gyF

rank

T. B

ergm

ann,

Her

bert

M. S

auro

FI79

G

ene

func

tion

pre

dict

ion

usin

g on

e-cl

ass

tech

niqu

eX

ian-

Min

g Z

hao,

Luo

nan

Che

n, K

azuy

uki A

ihar

a

Oth

ers

Oth

ers

OT01

A

ccur

ate

quan

tifi

cati

on o

f co

mpo

nent

sto

ichi

omet

ry o

f a

mul

tipr

otei

n co

mpl

ex b

y m

eans

of

mas

s sp

ectr

omet

ry w

ith

a pe

ptid

e-co

ncat

enat

ed s

tand

ard

prot

ein

Kei

ji K

ito,

Tom

oko

Fuj

ita,

Kaz

uhis

a O

ta, T

akas

hi I

to

OT02

S

yste

ms

mic

robi

olog

ical

inve

stig

atio

ns in

to th

e tw

o-co

mpo

nent

sys

tem

s in

E. c

oli

Jeon

g-R

ae K

im, H

youn

g-Se

ok C

hoi,

Jun

il K

im, D

ongs

an K

im, Y

eoin

Yoo

n,

Sang

-Woo

Lee

, Kw

ang-

Hyu

n C

ho

OT03

Fi

ndin

g hu

man

miR

NA

gen

es lo

cate

d w

ithin

pro

mot

er r

egio

ns a

nd a

ssoc

iate

d w

ith C

pG

isla

nds

Min

g-C

heng

Tsa

i, J

an-G

owth

Cha

ng, K

a-L

ok N

g

4848

Tutorials

Sunday, October 8

Venue: Pacifico Yokohama

Room 9:30-12:30 14:00-17:00

411+

412

T2: Structural and functional analysis of signaling networksSteffen Klamt, Julio Saez-Rodriguez (Max Planck Institute Magdeburg, Germany)

T4: Tutorial on the Systems Biology Toolbox for MATLAB Henning Schmidt (Fraunhofer Chalmers Research Centre)

413T1: Engineering design principles for biologistsKyaw Tun, (Univ.Singapore), Arun Krishnan (Keio Univ.), Pawan K Dhar (RIKEN GSC) (*2 hours)

T5: Pathway Modeling with Teranode XDAMike Kellen (Teranode)

414+

415

T3: New Mathematical Methods for Systems BiologyEric Mjolsness (UC Irvine)

416T12: The Systems Biology Markup Language (SBML) Level 2 Version 2Michael Hucka (California Institute of Technology)

T6: Analyzing Biochemical Systems using the E-Cell SystemSatya Arjunan (Keio University)

417T8: Modeling, simulating, and analyzing biochemical systems with CopasiPedro Mendes (Virginia Bioinformatics Institute)

T9: Advanced model analysis with CopasiPedro Mendes (Virginia Bioinformatics Institute)

418T11: Application of Experimental Design and Model Selection to Signal Transduction Pathway ModelingThomas Maiwald, Marcel Schilling, Sebastian Bohl(University of Freiburg, German Cancer Research Center ) (*1 day)

419T7: Computational Cell Biology with the Virtual CellIon I. Moraru and James C. Schaff (University of Connecticut Health Center)

T10: CellDesignerAkira Funahashi (The Systems Biology Institute/JST)

4949

Workshops

A. Systems Biology Graphical Notation (SBGN Workshop)Date: Saturday, October 7, 2006 09:30 – 18:00Venue: Yokohama World Porters Building (5 min. walk from Pacifico Yokohama)Organizers: Hiroaki Kitano (SBI & Sony CSL), Yukiko Matsuoka (SBI & JST), Akira Funahashi (SBI & JST), Michael Hucka (California Institute of Technology), Nicolas Le Novère (EBI)

B. RTK workshop: Receptor tyrosine kinases (RTK) training courseDate: Thursday-Friday, October 12-13 2006 09:15 – 17:30Venue: AIST Tokyo Waterfront Bio-IT Research Building, OdaibaOrganizers: RTK Consortium & RIKEN Genomic Sciences Center (GSC)

C. Systems Biology Markup Language (SBML) Forum Meeting; The 11th Workshop on Software Platforms for Systems BiologyDate: Thursday-Friday, October 12-13 2006 09:30 – 17:30Venue: National Museum of Emerging Science and Innovation “Miraikan”Organizers: Michael Hucka (California Institute of Technology), The Systems Biology Markup Language (SBML) Team

D. International Workshop on Synthetic Biology “Synthetic Approaches to Cellular Functions”Date: Thursday, October 12, 2006 09:30 – 18:00Venue: National Museum of Emerging Science and Innovation “Miraikan”Organizers: Daisuke Kiga (Tokyo Institute of Technology), Drew Endy (MIT), Vitor Martins dos Santos (German Research Centre for Biotechnology), Hiroki Ueda (RIKEN)

E. Systems Biology Workshop: “Systems Biology and the Human Health Risks of Environmental Chemicals”Date: Thursday, October 12, 2006 09:00 – 15:00Venue: National Museum of Emerging Science and Innovation “Miraikan”Organizers: Rory Conolly (U.S. Environmental Protection Agency)

RestroomsMultiple Use ToiletBabyʼs bedRefreshment AreaEscalators/StairsElevatorsRestaurant

Exhibition AreaResearchArea

LoungeInnovation Hall

Restaurant

Conference Room 2

Conference Room 1Conference Room 3

ABLNG

INH

HAL

CR2 CR1

CR3

MIRAICANHall

Floor Map, "Miraikan" (7F)

Venue Map (October 12-13 Workshops)

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5050

Access

lAnnex Hall

Bus/Large Vehicle Parking Lot

Kannai Area

Shinko Area

YokohamaPortside Area

Breezbay Hotel

On foot

YokohamaMuseum of Art

YokohamaMedia Tower

LeafMinato Mirai

HomecenterSekichu

Metropolitan Expressway(Yokohama-Haneda Line)Minato Mirai Ramp

Route16

1etu

oR

Yokohama Municipal Subway

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Yokohama Jackmall

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Post Office

Taxi Terminal

Yokohama-Minato MiraiManyo-club

Navios Yokohama

YokohamaCosmo World

JICA YokohamaInternational Center

Mitsubishi Heavy Industries Bldg.

JR LineSakuragicho Station

Sakuragicho Station

Bus Taxi Terminal

Cross GateYokokhamaSakuragichoWashinton Hotel

Pukarisanbashi PierSea Bass Terminal

Shinko Park

Unga Park

GENTOYOKOHAMA

Aka-Renga Soko

Aka-Renga Park

Shinko Pier

(Yokohama Red Brick Warehouse)

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Sea Bassto Yokohama

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Rinko Park

Rinko Park Parking Lot

Minato MiraiBusiness Square

Cross-Patio

Keiyu Hospital

Minato Mirai Sta.

Yokohama Sakuragi Post Office

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1-1-1 Minatomirai, Nishi-ku, Yokohama200-0012, JapanInformation TEL: +81(45)221-2155URL:http://www.pacifico.co.jp

P1

P1Annex HallExhibition Hall

Kokusai Odori Boulevard

NationalConvention Hallof Yokohama

Inter ContinentalThe Grand Yokohama

ConferenceCenter

To Parking

To Parking

r rHarbor Lounge

P1To Parking

World Porters

Moving Walkway

Shinagawa

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Tokyo

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Narita ExpressJR LineYurikamome

AirportTerminal 2 Stn.

NaritaAirport Stn.(Terminal 1)

NaritaAirport

Tokyo Bay

Akihabara

Shinbashi

National Museum of EmergingScience and Innovation (Miraikan)AIST/CBRC

Minato MiraiYokohama

PACIFICOYOKOHAMA

WorldPorters

Minato Mirai Line

(Odaiba Area)

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Sub Hall 1Sub Hall 1

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Tutorials (8th Oct.)Poster Sessions (9th, 10th Oct.)

Registration DeskICSB-2006 OfficePreview Room

Main HallSponsor Exhibitions

Sub Hall 2

Sub Hall 1

Poster Display

Registration DeskPreview Room

ICSB-2006 Office

Main Hall

Sponsor Exhibitions

© ICSB-2006 Conference Committee