Quantitative Studies of Nitrogen Assimilation & Its Control in Enteric Bacteria: From Molecules to Physiology

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Historically, metabolic systems have served as fertile breeding grounds for many important concepts of molecular biology, including the mechanisms of gene regulation and strategies of homeostasis. At the dawn of the era of systems biology, metabolic systems can play an especially important role towards establishing how system level properties may be quantitatively studied, since many of the components are already known and quantitatively characterized. In this research, a combined experimental and theoretical approach will be used to study the control of nitrogen assimilation and its coordination with carbon/energy metabolism in E. coli. Nitrogen assimilation is carried out by a very compact system consisted of just 3 key enzymes and 3 metabolites, but controlled by a network of regulatory proteins. The goal of this research is to link the biochemistry and molecular biology of the components to growth physiology. This will be accomplished by studying nitrogen flux under media with a spectrum of nitrogen and carbon availability; flux patterns obtained will then be related to the known biochemistry and molecular biology of the regulatory apparatus on the one hand, and to growth physiology on the other hand. The results are expected to produce a quantitative framework connecting the molecular control of nitrogen assimilation to growth physiology, thereby establishing a practical roadmap for extending this approach to other sectors of the metabolic network. Students involved in this project will be exposed to a tightly integrated interdisciplinary education and research experience involving biochemistry, molecular biology, computation, and microbial physiology.