QSB: Experimental Driven Computational Analysis of E. coli Global Redox Sensing/Regulatory Networks and Cellular Responses

该项目的总体目标是开发一个与现有的机理知识和精心设计的内部实验相一致的综合量化框架，用于研究和最终加强大肠杆菌氧气和氧化还原传感/调控系统。实验数据将从文献和研究人员的实验室获得。具体目标是：(1)构建可通过实验验证的氧和氧化还原传感/调控系统的遗传网络模型；(2)开发从(1)中实现的网络模型中提取代谢路径图的方案；(3)使用标准代谢通量分析技术根据预测的代谢路径图生成代谢模式；(4)构建用于生物反应器实验的突变菌株，以支持建模工作；以及(5)进行生物反应器实验，以产生用于完善和验证网络和路径模型的定量数据。

The overall objective of this project is to develop an integrated quantitative framework, consistent with existing mechanistic knowledge and well-designed in-house experiments, for the study and eventual enhancement of the Escherichia coli oxygen and redox sensing/regulatory system. Experimental data will be obtained from the literature and the investigators' laboratories. The specific goals are: (1) to construct an experimentally verifiable model of the genetic network of the oxygen and redox sensing/regulatory system; (2) to develop a scheme for distilling maps of metabolic pathways from the network models achieved in (1); (3) to generate metabolic patterns based on the predicted metabolic pathway maps using standard metabolic flux analysis techniques; (4) to construct mutant strains to be used in bioreactor experiments to support the modeling effort; and (5) to perform bioreactor experiments to generate quantitative data to be used to refine and validate the network and pathway models.