Quantitative Modeling of Bacterial Chemotaxis Signaling Pathway

描述（由申请人提供）：本研究项目的长期目标是实现对系统水平大肠杆菌趋化行为及其潜在分子水平机制的定量理解。我们将基于趋化性信号通路的结构和生化细节，开发蛋白质相互作用网络及其动力学的数学模型。这些模型将采用解析分析和数值模拟方法进行研究。这些模型的结果将用于解释实验数据并做出可测试的预测。模型与实验数据之间的迭代比较将用于改进/完善模型。在本文中，我们将重点研究大肠杆菌趋化途径的两个基本方面：1)趋化受体阵列的信号动力学和功能。我们将研究混合受体阵列如何区分不同的刺激（信号），以及细胞如何根据这些信息做出决定。我们想研究ATP水解在传感器激酶信号传导中的作用，以及它如何调节激酶对受体配体结合的反应敏感性。2)鞭毛运动的开关机制及其对机械信号的依赖。我们想要了解鞭毛马达是如何通过其机械环境（力，负载）的变化以及细胞内的化学信号来控制的。总之，我们计划调查和了解大肠杆菌细胞如何感知不同的（化学和物理）信号，它如何处理这些信息，以及它如何在具有多个时间变化线索的复杂环境中做出决定。

DESCRIPTION (provided by applicant): The long term goal of this research project is to achieve quantitative understandings of system-level E. coli chemotaxis behaviors and their underlying molecular level mechanisms. We will develop mathematical models of protein interaction network and its dynamics based on structural and biochemical details of the chemotaxis signaling pathway. These models will be studied by using analytical analysis and numerical simulation methods. The results from these models will be used to explain experimental data and make testable predictions. The iterative comparison between models and experimental data will be used to improve/refine the models. In this proposal, we will focus on studying two essential aspects of the E. coli chemotaxis pathway: 1) The signaling dynamics and function of the chemorecetor array. We will investigate how the mixed receptor array can distinguish different stimuli (signals) and how the cell makes decision based on the information. We want to study the effect of ATP hydrolysis in sensor kinase signaling and how it modulates the kinase response sensitivity to receptor ligand binding. 2) The switching mechanism for flagellar motor and its dependence on mechanical signals. We want to understand how the flagellar motor can be controlled by changes in its mechanical environment (force, load) in addition to the intracelur chemical signals. In summary, we plan to investigate and understand how an E. coli cell senses different (chemical and physical) signals, how it processes this information, and how it makes decisions in complex environments with multiple, time varying cues.