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Emergence de structures modulaires dans les régulations des systèmes biologiques : théorie et applications à Bacillus subtilis

Abstract : This thesis consist in studying the organization of the control system of metabolic pathways of bacteria to identify systemic properties revealing its operation. At first, we show that control of metabolic pathways is highly structured and can be decomposed into modules strongly decoupled in steady-state. These modules are defined by their singular mathematical properties having important implications in biology. This decomposition, based inherently on the system outlook of automatic control, offers a formal theoretical analysis of general control of metabolic pathways, which has been effective in analysing experimental data. In a second step, we consider the possible reasons for the emergence of this modular control structure. We identify a set of structural constraints acting at the distribution of a common resourc, the proteins between cellular processes. Satisfying these constraints for a given growth rate leads to formalize and to solve a non-differentiable convex optimization problem, that we call Resource Balance Analysis. This optimization problem is solved numerically at the scale of the bacteria through an equivalent linear programming problem. Several properties are derived from theoretical analysis of the obtained criterion. Firts, the growth rate is structurally limited by the distribution of a finite amount of proteines between the metabolic pathways and the ribosomes. Second, the emergence of modules in metabolic pathways arises from a policy of economy in proteins in the bacterium to increase the growth rate. Some well known transport strategies such as catabolite repression of the substitution between low/highaffinity transporters are predicted by our methods and could consequently be interpretd as ways to maximize growth while minimizing investment in proteins.
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Submitted on : Thursday, June 2, 2011 - 1:18:15 AM
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  • HAL Id : tel-00597796, version 1


Anne Goelzer. Emergence de structures modulaires dans les régulations des systèmes biologiques : théorie et applications à Bacillus subtilis. Sciences de l'ingénieur [physics]. Ecole Centrale de Lyon, 2010. Français. ⟨NNT : 2010ECDL0030⟩. ⟨tel-00597796⟩



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