The mechanistic basis for metabolic pathway evolution: the evolution of the corti

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DESCRIPTION (provided by applicant): While more cellular processes rely on specific interactions, the mechanisms by which these interactions evolve are unknown. Metabolic pathways, for example, control many cellular processes but how new enzymes are added to pathways and how the specific interactions between enzyme and substrate evolve are mostly unknown. This project will address these gaps in understanding by studying the evolution the corticosteroid metabolic pathway, which is responsible for regulating stress, salt balance, metabolism and other important physiological processes. This pathway is diverse among the vertebrates and the proteins in the pathway are biochemically tractable. I will use a combination of phylogenetics, biochemistry, biophysics and molecular biology to understand the mechanisms by which biosynthetic steps are added to existing metabolic networks, and how specificity arises to produce novel metabolic products.