Dynamics and mechanism of mechanical regulation of bacterial flagellar motor swit

描述（由申请方提供）：鞭毛旋转是细菌移动的主要机制之一，并且对于生物膜形成至关重要。许多细菌使用跨膜电化学梯度（H+或Na+）来驱动跨膜鞭毛马达的旋转。有广泛的，但单独的实验和建模工作的BFM转矩产生和CW-CCW开关。然而，最近贝格实验室观察到，电机开关动力学受到负载以及趋化信号的影响。电动机开关频率首先增加，但随后随着外部负载的增加而降低。这种现象被认为具有功能作用。理解这些结果需要统一处理转矩产生和切换。 在这项研究中，我们的目标是建立一个完整的模型，描述鞭毛电机开关和扭矩产生的基础上，现有的实验数据，有以下三个具体目标：1）构建一个数学模型，并检查机制的负载依赖开关动力学。我们将概括的构象传播模型，包括开关速率对电机转矩的依赖性，这是直接从测得的转矩-速度关系，并评估各种机制。初步研究证实了该程序的有效性。2)检查负载相关的开关动态可能的功能作用。我们将使用目标1和2中开发的模型来研究Chey-P浓度波动下的多电机动力学。拟议的研究将通过与霍华德贝格（哈佛大学）、难波庆一（大坂大学）、理查德贝瑞（牛津大学）和大卫布莱尔（犹他州大学）的实验室合作进行。相应的实验将在这些实验室进行。我们将系统地检查现有的实验结果，桥梁和整合静态结构信息和动态数据，并在其他几个实验室的实验研究并行可测试的预测。它将把BFM功能的研究放在细胞生理学调控的更广泛的背景下。

DESCRIPTION (provided by applicant): Flagellar rotation is one of the major mechanisms for bacterial mobility, and is essential for biofilm formation. Many bacteria use the transmembrane electrochemical gradient (H+ or Na+) to power rotation of the transmembrane flagellar motor. There are extensive but separate experimental and modeling efforts on BFM torque generation and CW-CCW switching. However, recently the Berg lab observed that the motor switch dynamics is affected by the load as well as chemotactic signals. A motor switching frequency increases first but then decreases upon increasing the external load. This phenomenon is suggested to have functional roles. Understanding these results requires a unified treatment of torque generation and switching. In this proposed research, we aim at constructing an integrated model describing flagellar motor switching and torque generation based on available experimental data, with the following three specific aims: 1) Construct a mathematical model and examine mechanism for the load-dependent switching dynamics. We will generalize the conformational spread model by including the dependence of switching rates on motor torque, which is obtained directly from the measured torque-speed relations, and evaluate various mechanisms. Preliminary studies have confirmed validity of the procedure. 2) Examine possible functional roles of load-dependent switching dynamics. We will use the models developed in Aim 1 and 2 to examine multi-motor dynamics under fluctuating CheY-P concentrations. The proposed research will be performed through collaborating with the labs of Howard Berg (Harvard University), Keiichi Namba (Osaka University), Richard Berry (Oxford University), and David Blair (University of Utah). Corresponding experiments will be performed in these labs. We will systematically examine the existing experimental results, bridge and integrate static structural information and dynamic data, and make testable predictions parallel to the experimental studies in several other labs. It will place studies of BFM functions in the broader context of cell physiology regulations.