Project funded in the
framework of the Action Concertée Incitative
IMPBio
The study of genetic regulatory networks has received a major impetus
from the recent development of experimental techniques allowing the
measurement of the spatio-temporal expression level of all genes in an
organism under different conditions. In addition to high-throughput
experimental methods, mathematical and computational approaches are
indispensable for the analysis of genetic regulatory networks. A
formalism based on piecewise-linear (PL) differential equations has
been shown to be particularly adapted to the modeling of these networks.
The aim of the project BacAttract, funded in the framework of the ACI IMPBio, is to theoretically and
experimentally analyze the dynamics of bacterial regulatory networks. In
the first part of the project, we will study the attractors of the PL
systems (equilibrium points and limit cycles), as well as their
stability and their basin of attraction. The results of these
mathematical studies will be used to develop efficient algorithms for
the identification of attractors of a model of a given model. These
algorithms will be implemented in a new module of Genetic Network Analyzer (GNA),
an existing tool for the qualitative
modeling and simulation of genetic regulatory networks.
In the second part of the project, the tool will be put to work in the
study of the networks implied in the global regulation of transcription
in the bacteria Escherichia coli
et Synechocystis PCC 6803. We
will develop the PL models of these networks by using data available in
the literature, supplemented by plausible hypotheses. The predictions of
the attractors, obtained by GNA from these models, will be
experimentally tested, by using measurements of the expression level of
the genes, the concentration of certain proteins and metabolites, as
well as the DNA topology.
At the time of writing (December 2004), the project is on schedule. An
article on the mathematical analysis of equilibrium points of PL
differential equations and their stability has been submitted, while a
prototype implementation of a module of GNA for the identification of
equilibrium points is currently in progress. An initial model of the
global regulation of transciption in E.
coli has been completed and is described in an article submitted
for publication. In order to test the model predictions, experiments to
measure the temporal expression profile of key genes have been
launched. In addition, a first model of the corresponding process
in Synechocystis is on the
point of being finished.
G. Batt, D. Ropers, H. de Jong, J. Geiselmann, M. Page, D.
Schneider (2004), Qualitative analysis and verification of hybrid
models of genetic regulatory networks: Nutritional stress response in Escherichia coli, Proceedings Hybrid Systems: Computation
and Control (HSCC 2005), LNCS, Springer-Verlag, Berlin, 2005, in
press.
H. de Jong (2003), BacAttract - Analyse théorique et
expérimentale d'attracteurs de réseaux de
régulation génique : régulation globale de la
transcription chez Escherichia coli
et Synechocystis PCC 6803, text of the proposition ACI IMPBio.
1. CEG (Laboratoire
Adaptation et Pathogénie des Microorganismes, CNRS UMR 5163,
université Joseph Fourier, Grenoble)
Participants in project: Estelle Crozat, Johannes Geiselmann,
Sylvain Lemeille, Nadège Philippe, Dominique Schneider.
Head of the group and adress:
Johannes Geiselmann, bâtiment Jean Roget, Faculté
de Médecine-Pharmacie, Domaine de la Merci, 38700 La Tronche. Telephone: 04 76 63 74 79 Email: Hans.Geiselmann@ujf-grenoble.fr Web
page: http://merci-gscol1.ujf-grenoble.fr/ijr/index.php
2.
COMORE (INRIA Sophia-Antipolis)
Participants in project: Olivier Bernard, Richard Casey, Jean-Luc
Gouzé. Head of the group and adress: Jean-Luc Gouzé, INRIA
Sophia-Antipolis, 2004 route des Lucioles, BP 93, 06902 Sophia-Antipolis
CEDEX. Telephone: 04 92 38 78 75 Email: gouze@sophia.inria.fr Web page: http://www-sop.inria.fr/comore/COMORE-fra.html
3.
HELIX (INRIA Rhône-Alpes)
Participants in project: Hidde de Jong, Michel Page, Delphine
Ropers. Head of the group and
address: François Rechenmann,
INRIA Rhône-Alpes, 655 avenue de l'Europe, Montbonnot, 38334 Saint
Ismier CEDEX. Telephone: 04 76 61 53 65 Email: francois.rechenmann@inrialpes.fr Web page: http://www-helix.inrialpes.fr/
4.
LMA (Université de Haute-Alsace, EA 1108, Mulhouse)
Participants in project: Tewfik Sari. Head of the group and adress: Tewfik Sari, Laboratoire de
Mathématiques et Applications, Université de Haute-Alsace,
4 rue des Frères Lumière, 68093, Mulhouse. Telephone: 03 89 33 63 47 Email: T.Sari@uha.fr Web page: http://www.math.univ-mulhouse.fr/
5.
TOP (Laboratoire Organismes Photosynthétiques et Environnement,
CNRS FRE 2433, École Normale Supérieure, Paris)
Participants in projet: Jean-Charles
Cadoret, Jean Houmard, Irène Perewoska, Gérald Zebulon.
Head of the group and adress: Jean
Houmard, département de biologie, École Normale
Supérieure, 46 rue d'Ulm, 75230 Paris Cedex 05. Telephone: 01 44 32 35 19 Email: jhoumard@biologie.ens.fr Web page: http://www.biologie.ens.fr/depbio/recherche.php.en
Agenda :
Réunion de
démarrage : 19 décembre 2003 (ENS Paris)
Réunion groupe de travail sur l'analyse dynamique de
réseaux de régulation biologique : 6-7 mai 2004 (INRIA
Grenoble)
Réunion technique : 10-11 juin 2004 (INRIA Sophia-Antipolis)
Réunion technique : 20-21 juillet 2004 (INRIA Grenoble)
Réunion technique : 1 octobre 2004 (INRIA Grenoble)
Réunion technique et réunion générale :
16-17 décembre 2004 (ENS Paris)
