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Proceedings of the Dieppe Spring School on Modelling and Simulation of Biological Processes in the Context of Genomics

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Proceedings of the Dieppe Spring School on Modelling and Simulation of Biological Processes in the Context of Genomics Proceedings of the Dieppe spring school on Modelling and simulation of biological processes in the context of genomics With the support of Genopole® May 12th to 16th 2003 Edited by: Patrick Amar, François Képès, Victor Norris, Philippe Tracqui FOREWORD The post-genomic era of biology is characterised by a deluge of molecular data about the cell. This ‘new’ biology has its own vocabulary of genome, transcriptome, proteome and even metabolome, interactome and lipidome. The challenge is to make sense out of this information by coming up with a new integrated picture of the cell which takes into account that it is simultaneously an autocatalytic set, a tensegrity structure, a network or a set of networks with particular connectivities and feedback characteristics, a set of codes and decoding devices, a self- organising system based on phase transitions, membrane physics, water structures and a host of physico-chemical properties of ions, polymers and other cellular constituents, a multi-level society adapted to the vagaries of an environment that can vary rapidly from heaven to hell … and so on. Taking on this challenge therefore also requires the introduction of concepts unfami- liar to biologists and the development of new ones, the formulation of new hypotheses and their testing via simulations or wet experiments. Taking on this challenge therefore requires specialists from across the sciences to learn each other’s language so as to collaborate effectively on defined projects. Just such a multi-disciplinary group of scientists has been meeting regularly at Genopole, a leading centre for genomics in France. This, the epigenomics group, is divided into four subgroups. The consensus subgroup has as one of its present objectives the interpretation of transcriptome data from micro-arrays obtained, for example, from the exposure of cells to low level pollutants or from cells as they progress through the cell cycle. The membranes and intracellular structures subgroup focuses on membrane deformations involved in the functioning of the Golgi, in cell division or in attachment to surfaces, on the dynamics of the cytoskeleton, and on the dynamics of hyperstructures (which are extended, multi-molecule assemblies that serve a particular function). The organisation subgroup has adopted a systems biology approach with the application and development of new programming languages to describe biological systems which it has been applying to problems in the growth and differentiation of plants and in the structure and functioning of mitochondria. The observability subgroup addresses the question of which models are coherent and how can they best be tested by applying a formal system, originally used for testing computer languages, to an epigenetic model for mucus production by Pseudomonas aeruginosa, the bacterium involved in cystic fibrosis. The work of these subgroups underpinned the first conference organised in Autrans in 2002. This work also underpinned the conference in Dieppe which, as reported here, brought together biologists, physical chemists, physicists, statisticians and computer scientists from both inside and outside the epigenomics group and gave leading specialists the opportunity to address an audience of doctoral and post-doctoral students as well as colleagues from other disciplines. These two first editions of the spring school in Autrans and Dieppe will be followed by others each year. Patrick Amar, Pascal Ballet, Gilles Bernot, Alessandra Carbone, Jean-Paul Comet, Franck Delaplace, Jean-Marc Delosme, Maurice Demarty, Marie Dutreix, Christine Froideveaux, Jean-Louis Giavitto, Christophe Godin, Misha Gromov, Janine Guespin, Roberto Incitti, Marcelline Kaufman, François Képès, Aurélien Mazurie, Olivier Michel, Jean-Pierre Nadal, Victor Norris, François Radvanyi, Alain Rambourg, Michel Thellier, Philippe Tracqui, Abdallah Zemirline. ACKNOWLEDGMENTS We would like to thank the seminar participants, who have contributed in a way or another to this book. It gathers overviews of the talks, discussions and roundtables, original articles contributed by speakers, abstracts from attendees, and courses proposed by the epigenesis group to review or illustrate matters related to the scientific topics of the seminar. Of course, the organisation team would like to express gratitude to all the staff of the Hotel La Présidence for the very good conditions we have found during the seminar. Special thanks go to Hélène Pollard (directrice de Genopole Recherche) and Catherine Meignen (chargée de l’organisation des manifestations scientifiques à Genopole Recherche) for their help during the preparation of the spring school and for their assistance in preparing this book for publication. We would like to thank Paul Hossenlopp (responsable de la formation cellule de la politique de l’Emploi, CNRS) for his encouragement to this spring school and for his support to the organisation of the next editions of this school. We would also like to express our thanks to the sponsors of this seminar for their financial support allowing the participants to share their enthusiasm and ideas in such a constructive way. They were: ® • Genopole Évry (http://www.genopole.org), • Centre National de la Recherche Scientifique - CNRS (http://www.cnrs.fr), • LaMI - Université d’Evry (http://www.lami.univ-evry.fr), • Institut National de la Recherche Agronomique - INRA (http://www.inra.fr), • Région Haute Normandie (http://www.region-haute-normandie.fr), • Fondation Scientifique Fourmentin-Guilbert (http://www.fourmentinguilbert.org), • Centre Interdisciplinaire de Biologie Intégrative and Université de Rouen (http://www.univ-rouen.fr), • Société Francophone de Biologie Théorique - SFBT (http://sfbt.org). The editors Patrick Amar, François Képès, Vic Norris and Philippe Tracqui CONTENTS PART 1 - CONFERENCE SYNTHESIS PART 2 - ARTICLES BioDyn: a Software for Cell Physiology PASCAL BALLET, ABDALLAH ZERMILINE, LIONEL MARCÉ Chromatin dynamics are a hyperstructure of nuclear organization ARNDT BENECKE Modelling and simulation of large assemblies of proteins PATRICK AMAR, GILLES BERNOT, VICTOR NORRIS Modelling, observability and experiment: a case study GILLES BERNOT, JANINE GUESPIN-MICHEL, JEAN-PAUL COMET, PATRICK AMAR, ABDALLAH ZEMIRLINE, FRANCK DELAPLACE, PASCAL BALLET, ADRIEN RICHARD Models of biological pattern formation HANS MEINHARDT Storage and recall of morphogenetic signals in plants MICHEL THELLIER Using an attribute estimation technique for the analysis of microarray data JEREMY MARY, GERALDINE MERCIER, JEAN-PAUL COMET, ANTOINE CORNUÉJOLS, CHRISTINE FROIDEVAUX & MARIE DUTREIX Physico-chemical aspects of the bacterial genome SÓNIA CUNHA, THEO ODIJK, NORBERT O. E. VISCHER, S. ELMORE & CONRAD L. WOLDRINGH Interfacial water: a modulator of the biological activity PASCALE MENTRÉ Hybrid system to model biological objects: application to mitochondria organelle MARIE BEURTON-AIMAR, SABINE PÉRES, PASCAL BALLET, ABDALLAH ZEMIRLINE, CHRISTINE NAZARET & JEAN-PIERRE MAZAT Questions for cell cyclists VICTOR NORRIS, ANTHONY DELAUNE, CEDRIC DERUE, ARMELLE CABIN-FLAMAN, MAURICE DEMARTY, YOHANN GRONDIN, GUILLAUME LEGENT, CHANTAL MONNIER , HELENE POLLARD & DEREK RAINE PART 3 - CONFERENCE SCHEDULE PART 4 - LECTURES / ABSTRACTS From cells to bioinformatics FRANÇOIS KÉPÈS From transcriptome to transcriptional regulatory networks BERNARD VANDENBUNDER Order and disorder in bacterial genomes EDUARDO ROCHA Cellular migration and extra cellular remodelling GEORGIA BARLOVATZ-MEIMON About commandability, observability and identifiablility of systems DANIEL CLAUDE Introduction to temporal logic and model-checking GILLES BERNOT Epigenesis and validation JANINE GUESPIN-MICHEL Organisation of the yeast proteome BERTRAND SÉRAPHIN The nucleolus: functions and assembly DANIÈLE HERNANDEZ-VERDUN Integration of the splicing process of ARNs in the cell and the nucleus BERTRAND SÉRAPHIN Dynamics of membranes CHAOUQI MISBAH Tensegrity behaviour of cortical and cytosolic cytoskeletal components in twisted living adherent cells VALERIE LAURENT, PATRICK CAÑADAS, REDOUANE FODIL, EMMANUELLE PLANUS, ATEF ASNACIOS, SYLVIE WENDLING, DANIEL ISABEY Modelling of the early phases of haematopoiesis JEAN-PIERRE VANNIER A PK/PD model of aminoglycoside nephrotoxicity DANIEL CLAUDE Organ initiation at the shoot apical meristem in higher plants: dynamics of a stable system JAN TRAAS, PIERRE BARBIER DE REUILLE, CHRISTOPHE GODIN Modelling biological systems in constraint programming ALEXANDER BOCKMAYR Simulation of the bacterial in vivo ERIC FOURMENTIN-GUILBERT Water at interfaces: from model systems to biomolecules MARIE-CLAIRE BELLISSENT-FUNEL PART 5 - POSTERS Modelling of the MAPK pathways by a fuzzy inference graph for the multi-agents simulations GABRIEL QUERREC, VINCENT RODIN, JEAN-FRANÇOIS ABGRALL, JACQUES TISSEAU Towards a dynamic model of the Arabidospsis' Meristem PIERRE BARBIER DE REUILLE, JAN TRAAS, CHRISTOPHE GODIN Models of circadian clocks in the cell and the nucleous PAUL FRANÇOIS, VINCENT HAKIM A formal framework for the modelling of biological regulatory networks VINCENT BASSANO, GILLES BERNOT A model of genetic regulation for the variation of mRNA expression DEREK J. RAINE, YOHANN GRONDIN PART 6 - HIGH LEVEL COURSES Hyperstructures VICTOR NORRIS, PATRICK AMAR, PASCAL BALLET, GILLES BERNOT, FRANCK DELAPLACE, MAURICE. DEMARTY, JEAN LOUIS GIAVITTO, CAMILLE RIPOLL, MICHEL THELLIER, ABDALLAH ZEMIRLINE Emergent features of cell structural dynamics: a review of models based on tensegrity and nonlinear oscillations
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