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Scalable modelling and analysis techniques to study emergent cell behaviour -- understanding the E. coli stress response

Objective

The aim of our research is to enhance our understanding of the molecular mechanisms underlying the behavior of complex living systems. In particular, we investigate how large and complex regulatory networks control the response of a living cell to its ever-changing environment.

The stress response to environmental events is induced by the interaction of several interwoven modules with complex dynamic behavior, acting on different time scales. To deal with this complexity we need mathematical modeling and computer-supported analysis. So far, the methods of systems biology are mostly applied to individual modules, such as particular metabolic pathways and genetic networks. But to understand the global behavior, we need an integrated description of the regulatory network. We must develop new, scalable methods for modeling and analysis of integrated networks.

We will apply our methods to the stress response system of the enterobacterium Escherichia coli, one of the best-studied organisms and a model for several pathogenic bacteria. In the project, we will develop an integrated model of the stress response system of E. coli, including key metabolic, genetic and signaling modules. We also develop methods to reduce high-dimensional nonlinear systems of equations, and to approximate them by discrete automata. Parallel model checking algorithms will be developed for verifying specific properties at the model. So we can explore the models and predict the outcome of experiments.

Finally, we will validate our model by experimentally testing predicted properties in our labs. Our cross-disciplinary European team of biologists, mathematicians and computer scientists will develop a coherent and generic methodology, generalizable to other complex (biological) systems. Our models will be accessible via the Silicon Cell and the International E. coli Alliance. They could improve many medical and biotechnological applications, e.g. strain improvement and rational drug design.

Call for proposal

FP6-2005-NEST-PATH
See other projects for this call

Funding Scheme

STREP - Specific Targeted Research Project

Coordinator

UNIVERSITEIT TWENTE
Address
Drienerlolaan 5
217 Enschede
Netherlands

Participants (6)

INSTITUT NATIONAL DE RECHERCHE EN INFORMATIQUE ET EN AUTOMATIQUE
France
Address
Domaine De Voluceau - Rocquencourt
BP 105 Le Chesnay
VRIJE UNIVERSITEIT AMSTERDAM
Netherlands
Address
De Boelelaan 1105
Amsterdam
UNIVERSITY JOSEPH FOURIER - GRENOBLE 1
France
Address
621 Avenue Centrale - Domaine Universitaire
Grenoble
MASARYKOVA UNIVERZITA
Czechia
Address
Zerotinovo Nam. 9
Brno
THE UNIVERSITY OF EDINBURGH
United Kingdom
Address
Old College, South Bridge
Edinburgh
STICHTING CENTRUM VOOR WISKUNDE EN INFORMATICA
Netherlands
Address
Kruislaan 413
94079 Amsterdam