The overall aim is to elucidate the operating and design principles of metabolic and genetic networks. Two complementary strategies will be merged. The first is a theoretical analysis of small, modular pathways, which form the building blocks of biochemical systems, and of composites of these modules. The analysis will elucidate the dynamic activation profiles of enzymes that yield optimal responses to demands like brief peak availability of a metabolite or sustained change in metabolite composition. The second strategy will entail reconstituting sphingolipid metabolism in E. coli and using this as an experimental model for studying fluxes and the effects of specific regulatory interventions. The system thus has the potential to provide an in vivo laboratory for studying de novo pathway design.
