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

氮同化的定量研究

• 批准号: 0746581
• 负责人: Terence Hwa
• 金额: --
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0746581&HistoricalAwards=false
• 关键词: Quantitative; Studies; Nitrogen; Assimilation; &amp

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.

从历史上看，代谢系统一直是分子生物学许多重要概念的沃土，包括基因调控机制和体内平衡策略。在系统生物学时代的初期，代谢系统在确定如何定量研究系统水平特性方面可以发挥特别重要的作用，因为许多成分已经已知并进行了定量表征。在本研究中，将采用实验和理论相结合的方法来研究大肠杆菌中氮同化的控制及其与碳/能量代谢的协调。氮同化是通过一个非常紧凑的系统进行的，该系统仅由 3 种关键酶和 3 种代谢物组成，但由调节蛋白网络控制。这项研究的目标是将成分的生物化学和分子生物学与生长生理学联系起来。这将通过研究具有一系列氮和碳可用性的介质下的氮通量来实现；获得的通量模式将一方面与调节装置的已知生物化学和分子生物学相关，另一方面与生长生理学相关。预计结果将产生一个将氮同化的分子控制与生长生理学联系起来的定量框架，从而建立一个实用的路线图，将该方法扩展到代谢网络的其他部分。参与该项目的学生将获得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。