BacAttract - Theoretical and Experimental Analysis of Attractors of Genetic Regulatory Networks

 Global Regulation of Transcription in Escherichia coli and Synechocystis PCC 6803

French version  frenchflag

Coordinator : Hidde de Jong

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.

Several participants in the project are also implied in the project "GDyn : Analyse dynamique de réseaux de régulation génique", funded in the framework of the Actions de Recherche Coopérative (ARC)  of INRIA.

Contact: Hidde.de-Jong@inrialpes.fr

Information on the project

Documents  and publications: more information...

Groups: the participants and how to reach them...

Agenda: meetings, news, ...

Documents and publications :

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.

R. Casey, H. de Jong, J.-L. Gouzé (2004), Piecewise-linear models of genetic regulatory networks: Equilibria and their stability, INRIA RR-5353, submitted for publication.

D. Ropers, H. de Jong, M. Page, D. Schneider, J. Geiselmann (2004), Qualitative simulation of the nutritional stress response in Escherichia coli, INRIA RR-5412, submitted for publication.

H. de Jong, J. Geiselmann (2004), Modélisation et simulation de réseaux de régulation génique par des équations différentielles ordinaires, J.-F. Boulicaut, O. Gandrillon (eds), Informatique pour l'analyse du transcriptome, Hermès, Paris, 143-185.

H. de Jong, J. Geiselmann (2004), Modeling and simulation of genetic regulatory networks by ordinary differential equations, J. Chen, E.R. Dougherty, I. Shmulevich, Z.J. Wang (eds), Genomic Signal Processing and Statistics, Hindawi Publishing Corporation, Sylvania, OH, in press.


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)