Section: Overall Objectives

Overview

When confronted with changing environmental conditions, bacteria and other single-cell organisms have a remarkable capacity to rapidly adapt their functioning. The stress responses of bacteria are controlled on the molecular level by large and complex networks of interactions that involve genes, mRNAs, proteins, small effector molecules, and metabolites. The study of bacterial stress response networks requires experimental tools for mapping the interaction structure of the networks and measuring the dynamics of cellular processes. In addition, when dealing with systems of this size and complexity, we need mathematical modeling and computer simulation to integrate available biological data, and understand and predict the dynamics of the system under various physiological and genetic perturbations. 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.

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 adaptive capacities of E. coli in situations of nutritional stress is a necessary prerequisite for interfering with the cellular responses by specific perturbations or by even rewiring the underlying regulatory networks. This is the second and most ambitious aim of the project. It does not only spawn fundamental research on the control of living matter, but may ultimately also lead to practical applications. Because E. coli is easy to manipulate in the laboratory, it serves as a model for many pathogenic bacteria and is widely used in biotechnology, for such diverse applications as the development of vaccines, the mass production of enzymes and other (heterologous) proteins, and the production of biofuels.

The aims of IBIS raise four main challenges that generate new problems on the interface of biology, applied mathematics, and computer science. In particular, the success of the project critically depends on (1) the modeling of large and complex bacterial regulatory networks, (2) the computer analysis and simulation of the network dynamics by means of these models, (3) high-precision and real-time measurements of gene expression to validate the models, and (4) the control and re-engineering of bacterial regulatory networks. While the first three items have been active research topics over the past few years, the control of regulatory networks is a novel challenge for IBIS that will be developed in the coming years.

The challenges of the research programme of the IBIS team require a wide range of competences on the interface of (experimental) biology, applied mathematics, and computer science. Since no single person can be expected to possess all of these competences, the international trend in systems biology is to join researchers from different disciplines into a single group. In line with this development, the IBIS team is a merger of a microbiology and molecular genetics group on the one hand, and a bioinformatics and mathematical biology group on the other hand. In particular, the IBIS team is composed of members of the group of Johannes Geiselmann at the Laboratoire Adaptation et Pathogénicité des Microorganismes of the Université Joseph Fourier (UJF, CNRS UMR 5163), and the network modeling and simulation group formerly part of the HELIX project-team at INRIA Grenoble - Rhône-Alpes, a group coordinated by Hidde de Jong. Both groups include researchers and technicians from other institutes, such as CNRS and the Université Pierre Mendès France (UPMF). The two groups have established a fruitful collaboration, which has resulted in more than 40 peer-reviewed publications in journals, conferences, and books since 2000.(See http://ibis.inrialpes.fr for a complete list.)

Hidde de Jong is the head of the IBIS team and Johannes Geiselmann its co-director. The experimental component of IBIS also remains part of the Laboratoire Adaptation et Pathogénicité des Microorganismes, and Johannes Geiselmann continues to represent this group in the interactions with the laboratory and university administration.

Figure 1. The ibis was 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. Here Thoth is shown in human form with the face of an ibis. (Sources: http://en.wikipedia.org/wiki/Ibis , http://en.wikipedia.org/wiki/Thoth , and http://www.shoarns.com ).