Regulation and coordination in cellular metabolism

27 Sep 2013

Joshua Rabinowitz
Department of Chemistry and Integrative Genomics
Princeton University

Abstract

Metabolism, ie: the conversion of nutrient inputs into energy and building blocks, is of great industrial and medical importance. Compared to other complex biological processes, metabolism is the most rigorously chemically characterized. The connections between metabolites are enzyme catalyzed reactions, most of which have been known for more than half a century. Building from this core knowledge, my research focuses on how metabolic pathways work in concert to meet cellular requirements for survival and growth. My lab has developed quantitative tools for measuring many metabolites and associated reaction fluxes, and for deriving conceptual understanding from the resulting data. Using results from a variety of cellular model systems, I will discuss the following questions. What regulatory objectives can be achieved by feedback inhibition? When are other regulatory strategies required? And, for cofactors such as NADPH that can be made by many different pathways, how is total production coordinated with demand? Investigation of these questions is revealing new pathway functions and regulatory motifs of relevance to both metabolic engineering and disease treatment.

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