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Ibis : Modeling, simulation, measurement, and control of bacterial regulatory networks


Overview

Bacteria provide fascinating examples of the strategies developed by single-cell organisms to survive under environmental stresses. Stress responses of bacteria are controlled by large and complex networks of molecular interactions that involve genes, mRNAs, proteins, small effector molecules, and metabolites. The study of bacterial stress response networks requires experimental tools for characterizing the interactions making up the networks and measuring the dynamics of cellular processes on the molecular level. In addition, when dealing with systems of this size and complexity, we need mathematical modelling and computer simulation to integrate available biological data, and understand and predict the dynamics of the system under various environmental and physiological conditions. The analysis of living systems through the combined application of experimental and computational methods has gathered momentum in recent years under the name of systems biology.

Growing colony of E. coli cells.
Growing colony of E. coli cells.
Source : Stewart et al. (2003), PLoS Biol., 3(2) :e45.

The first aim of the Ibis team is the unravelling of bacterial survival strategies through a systems-biology approach, making use of both models and experiments. In particular, we focus on the enterobacterium Escherichia coli, for which enormous amounts of genomic, genetic, biochemical and physiological data have been accumulated over the past decades. A better understanding of the survival strategies of E. coli in situations of nutritional stress is a necessary prerequisite for interfering with these strategies by specific external perturbations or by the rewiring the underlying regulatory networks. This is the second and most ambitious aim of the research programme, which does not only spawn fundamental research on the control of living matter, but which may ultimately acquire medical relevance since E. coli serves as a model for many pathogenic bacteria.

Research challenges

The aims of Ibis raise five main challenges that generate new problems on the interface of (experimental) biology, applied mathematics, and computer science. In particular, the success of the project critically depends on :

- the modeling of large and complex bacterial regulatory networks

- the simulation of the network dynamics by means of these models

- high-precision and real-time measurements of gene expression and metabolism

- the use of these data for model validation and identification

- the control and re-engineering of bacterial regulatory networks

Partners

Ibis is a joint team of researchers affiliated with INRIA Grenoble - Rhône-Alpes (formerly in the Helix team) and the Laboratory Adaptation et Pathogénie des Microorganismes (CNRS UMR 5163) at the Université Joseph Fourier. Ibis is bilocated at INRIA Grenoble - Rhône-Alpes in Montbonnot and the Institut Jean Roget in La Tronche.

International relations

- Instituto Superior Tecnico, Lisbon, Portugal

- National University of Taiwan

- University of Pavia, Italy

- European project Hygeia

- European project EC-MOAN

- European project COBIOS

Industrial relations

- Genostar SA

Ibis

According to folklore, the ibis is the last form of wildlife to take shelter prior to a hurricane and the first to reappear after the storm passes. The ibis was also an object of religious veneration in ancient Egypt, particularly associated with the god Thoth. Thoth was seen, among other things, as a god of the measurement and regulation of events. In the picture below, Thoth is shown in human form with the face of an ibis.

Ibis and Thoth
Ibis and Thoth
Sources : Wikipedia and Shoarns.


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