Dynamics and mechanism of mechanical regulation of bacterial flagellar motor swit

细菌鞭毛运动开关的机械调节动力学及机制

基本信息

批准号：
8423015
负责人：
Jianhua Xing
金额：
$ 7.4万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-03-01 至 2015-02-28
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：鞭毛旋转是细菌移动的主要机制之一，对于生物膜的形成至关重要。许多细菌利用跨膜电化学梯度（H+或Na+）为跨膜鞭毛马达的旋转提供动力。关于 BFM 扭矩生成和 CW-CCW 切换有广泛但独立的实验和建模工作。然而，最近伯格实验室观察到，电机开关动力学受到负载和趋化信号的影响。当外部负载增加时，电机开关频率首先增加，然后减少。这种现象被认为具有功能性作用。了解这些结果需要对扭矩产生和切换进行统一处理。在这项研究中，我们的目标是根据现有的实验数据构建一个描述鞭毛电机切换和扭矩生成的集成模型，具有以下三个具体目标：1）构建数学模型并检查负载相关切换动力学的机制。我们将通过包括切换速率对电机扭矩的依赖性（直接从测量的扭矩-速度关系获得）来概括构象扩散模型，并评估各种机制。初步研究已证实该程序的有效性。 2) 检查负载相关开关动态的可能功能作用。我们将使用目标 1 和 2 中开发的模型来检查 CheY-P 浓度波动下的多电机动力学。拟议的研究将通过与 Howard Berg（哈佛大学）、Keiichi Namba（大阪大学）、Richard Berry（牛津大学）和 David Blair（犹他大学）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，桥接和整合静态结构信息和动态数据，并与其他几个实验室的实验研究并行地做出可测试的预测。它将把 BFM 功能的研究置于更广泛的细胞生理学调控背景下。