Section: New Results

Systems Biology

In her thesis, M. Behzadi has developed a know-how on the behaviour of biological systems along a cooperation with an Inserm-Inra team based in Clermont-Ferrand. In the methodology that was developed, one computes the equations' parameters from the experimental data in systems that can be considered at equilibrium. It was proved mathematically that some sub-domains are intrinsically stable and that their behaviour is not much affected by the initial conditions [4] for phospholipids biosynthesis. A review for carbone toxicity can also be found in [15] . Software Analyser software (Mpsa ) are currently under development by L. Paulevé.

Elementary flux mode is a fundamental concept as well as a useful tool in metabolic pathway analysis. However, when the networks are complex, the determination of elementary flux modes leads to combinatorial explosion of their number which prevents from drawing simple conclusions from their analysis. To deal with this problem, a biclustering method has developed [18] based on the Agglomeration of Common Motifs (ACoM). It was applied to the central carbon metabolism in Bacillus subtilis and to the yeast mitochondrial energy metabolism. It helped to give biological meaning to the different elementary flux modes and to the relatedness between reactions.

Once molecules and complexes participating in the signalling network have been identified, the relations between them (enzymatic reactions, activations, inhibitions, etc.) have to be deduced from experimental and literature data to build the influence graph. Partners Inra-Bios and Amib have started the development of a knowledge-based method, which uses the solver Solar , developed by NII (Tokyo), that allows automating this data integration task. We have already formalized the knowledge necessary for inferring the signalling network triggered by the FSH receptor, one famous GPCR. Preliminary results of this project Asam are very encouraging.