Section: Partnerships and Cooperations

National Initiative

Evolution of bacterial genomes

Participants : Guillaume Beslon, Stephan Fischer, Carole Knibbe, David P. Parsons, Bérénice Batut.

Our work on the Aevol software has received two interdisciplinary grants from the CNRS: an inter-institute grant (PEPII) and a grant from the INS2I institute (PEPS). In both cases, the objective is to trigger collaborations with other computer science teams, life science teams or mathematicians. In the case of the PEPS project, our collaborators are the LIP (Lyon) and LAPM (Grenoble). In the case of the PEPII project, we collaborate with the LIP (Lyon), LAPM (Grenoble), LBBE (Lyon) and ICJ (Lyon).

ColAge

Participants : Hugues Berry, Anne-Sophie Coquel.

ColAge is a 4-year research project launched in early 2009 as a Large-Scale Initiative Action co-funded by the French national research institutes INRIA (computer science) and Inserm (medicine and health). We search for natural and engineering solutions to the control of bacterial growth and aging using both systems biology and synthetic biology approaches. Our main strategy is to leverage synergies resulting from day-to-day collaborations between computer scientists and cell biologists. The research topics on aging in bacteria above is one of the ColAge workpackages. Supervisor: H. Berry, EPI Beagle. Total amount funded (for 2009-2010): 330,000 euros. Further information available at http://colage.saclay.inria.fr/ .

In 2010, ColAge fostered the emergence of two other grants/funding by the French national agency for research, ANR: Pagdeg (leaded by A. Lindner, see below) and GeMCo (leaded by M. Chaves, http://www-sop.inria.fr/members/Madalena.Chaves/ ).

PAGDEG

Participants : Hugues Berry, Anne-Sophie Coquel, Ariel Lindner, Y. Chen, L. Moisan.

A three-year project (2010-2012) funded by the French National Agency for Research (ANR), Call “PIRIBIO 2009” (Programme interdisciplinaire de recherche sur les systèmes moléculaires et cellulaires et d'innovation biomédicale). We study the causes and consequences of protein aggregation in cellular degeneration in bacteria combining innovative experimental (microfluidics, quantitative biology) and computer simulation (individual based-modeling, ODEs) approaches. Supervisor: A. Lindner (INSERM, Paris). Total amount funded: 450,000 euros.

Stochagene

Participants : Hugues Berry, Guillaume Beslon, Gaël Kaneko.

Stochagene is four-year project (2011-2015) funded by the French National Agency for Research (ANR), Call “Blanc 2011”. The objective of the project is to identify the molecular causes of stochasticity in gene expression by experimental and modeling approaches. Supervisor: O. Gandrillon (CNRS, Lyon). Total amount funded: 466,000 euros.

NéoBG (pour une théorie biologiquement réaliste de l’apprentissage par renforcement)

Participants : Hugues Berry, Jules Lallouette.

NéoBG in an interdisciplinary project funded by the CNRS (Appel Projets exploratoires pluridisciplinaires inter-instituts – PEPII – 2011-2012). Total amount funded for Beagle: 6 000€

Partnership with F. Taddei's group, INSERM U1001, Cochin hospital Paris

Participants : Guillaume Beslon, Carole Knibbe, David P. Parsons, Hugues Berry, Anne-Sophie Coquel.

Strong collaboration links exist between Beagle and F. Taddei's and A. Lindner's group, in Paris: First, A. Lindner and H. Berry collaborate on the study of aging in bacteria. Both co-supervise A.S. Coquel's PhD within grants ColAge and Pagdeg (see above). Moreover, Aevol, a software developed by our team (see above), is used by the INSERM experimentalist group in Paris: with our help, D. Misevic and F. Taddei use it to study the evolution of cooperation in bacteria: Under which conditions can cooperation emerge? What kind of genetic architecture evolves when cooperation arises?

Partnership with D. Schneider's group, LAPM, Univ. Joseph Fourier, Grenoble

Participants : Guillaume Beslon, Stephan Fischer, Carole Knibbe, David P. Parsons, Bérénice Batut.

The team of Dominique Schneider is composed of life scientists developing experimental evolution strategies with micro-organisms. We are engaged in a close collaboration with this team since the methodology they use is very similar to the one we develop with aevol (though they are studying real organisms). Several projects have been submitted this year (ANR, Labex, Investissement d'avenir en bioinformatique) and we are waiting for the results.

Astrocytic regulation of neuronal network activity

Participants : Hugues Berry, Jules Lallouette.

Research Networks Program in Computational Neurosciences and Computational Cognitive Sciences of the High Council for Scientific and Technological Cooperation between France-Israel. Total amount funded for Beagle: 80 000 €.

Healthy functionality of the central nervous system (CNS) relies on intricate neuron-glia networks. Recent data suggest that glial cells, including astrocytes, play a crucial role in the way information is processed and stored by the brain. In particular, synapses should not be considered bipartite, but rather tripartite structures, comprised of the pre-synaptic terminal, the post-synaptic one and the surrounding astrocyte. Moreover, glial cells, like neurons, also form intricate networks of cells and are linked by gap junctions to afford long-range communication via the propagation of calcium waves. Therefore, neurons and astrocytes form intertwined neuron-glial networks supporting active partnership between the two cell populations. Hence, understanding the nature of the neuron-glia interaction is essential to fully understand how the brain functions, and will serve as a stepping stone for deciphering disorders of the CNS. Our long-term goal is to reveal the underlying mechanism that controls and regulates the activity of combined neuron-glia networks. The specific objectives of this application, which are fundamental in the pursuit of that goal, are (1) to determine the properties of astrocytic calcium wave propagation and (2) to reveal how astrocyte signals dynamically affect synaptic information transfer, thus regulating neuronal network activity. To achieve these objectives we will employ a methodology that combines corresponding theoretical and experimental investigations of small neuron-glial networks. We will use unique cortical cultures made of several hundred well-identified cells, thus facilitating very systematic investigation in a manner that is fully compatible with our analytical tools. The significance of understanding glia-neuron interactions is several-fold as it pertains to a very wide range of applications, from basic understanding of neuronal activity, to developing therapeutic strategies toward the treatment of neurological disorders. Here, we will focus on ataxia-telangiectasia (A-T), a progressive neurodegenerative disorder induced by mutations in the ATM gene encoding the protein kinase ATM, a key player in the DNA damage response. Leveraging the possibilities offered by our joint experimental and theoretical approach, we will be able to investigate heterogeneous neuron-glial networks where one element comes from a diseased mouse model and the other from healthy (WT) animals. This novel approach will provide us with a unique opportunity to uncover the cellular origin of these pathologies.