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

从历史上看，代谢系统已经成为许多重要分子生物学概念的肥沃温床，包括基因调控机制和体内平衡策略。在系统生物学时代的黎明，代谢系统可以在建立如何定量研究系统级特性方面发挥特别重要的作用，因为许多成分已经已知并定量表征。本研究将采用实验与理论相结合的方法研究大肠杆菌中氮同化的控制及其与碳/能量代谢的协调。氮的同化是由一个非常紧凑的系统完成的，这个系统只由3种关键酶和3种代谢物组成，但由一个调节蛋白网络控制。本研究的目的是将这些成分的生物化学和分子生物学与生长生理学联系起来。这将通过研究具有氮和碳可用性谱的介质下的氮通量来实现；获得的通量模式将与已知的生物化学和调节装置的分子生物学有关，另一方面与生长生理学有关。这些结果有望产生一个定量框架，将氮同化的分子控制与生长生理学联系起来，从而建立一个实用的路线图，将这种方法扩展到代谢网络的其他部门。参与该项目的学生将接触到紧密结合的跨学科教育和研究经验，涉及生物化学，分子生物学，计算和微生物生理学。

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.