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Identifying the mechanisms of mechanosensing by the bacterial flagellar motor

识别细菌鞭毛马达的机械传感机制

基本信息

批准号：
10241543
负责人：
Navish Wadhwa
金额：
$ 10万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10241543
关键词：
Address Affect Bacteria Bacterial Infections Behavior Binding Biochemical Biology Biophysics Cell Wall Complex Data Filament Genetic Goals Image Infection K-Series Research Career Programs Lead Link Liquid substance Measures Mechanical Stimulation Mechanics Mediating Membrane Potentials Mentored Clinical Scientist Development Award (K08)Mentors Microbial Biofilms Molecular Motor Optics Outcome Output Pathway interactions Peptidoglycan Periodicity Polymers Positioning Attribute Preventive Process Regulation Research Second Messenger Systems Side Signal Pathway Signal Transduction Statistical Models Surface Swimming Testing Therapeutic Tissues Torque Training Virulence Factors Work bacterial genetics biophysical techniques cell motility diguanylate cyclase extracellular genomic tools imaging genetics improved individual response mechanical force mechanical load mechanotransduction molecular imaging novel novel therapeutic intervention prevent response self assembly sensor single molecule skills stoichiometry tool transposon sequencing

项目摘要

PROJECT SUMMARY/ABSTRACT Surface colonization in the form of biofilms or swarms by otherwise free-swimming bacteria is the first step in many bacterial infections, but how bacteria sense surfaces remains unknown. The bacterial flagellar motor has emerged as a key player in surface sensing. Seen traditionally as involved only in motility by rotating helical filaments, new evidence suggests that the motor acts as a mechanosensor to sense bacterial surface interactions. However, the components of the motor-mediated mechanosensing pathway largely remain unidentified. To develop effective strategies for preventing and treating harmful biofilms, there is a critical need to understand how the motor senses forces and transmits information to downstream processes. The objective of this proposal is to characterize the function of motor-mediated mechanosensing and its associated circuitry. The proposed work will utilize novel biophysical methods to precisely control the mechanical load acting on the motor and to measure the motor’s response. Previous results and preliminary data show that the motor adapts to load by changing its torque output via the dynamic self-assembly of torque-generating stator units, providing a possible mechanism for mechanoreception. On the signal transduction side, it is unclear how the mechanosensing information is transmitted from the motor to the biofilm formation pathways, which are regulated by the bacterial second messenger cyclic diguanylate (c-di-GMP). The central hypothesis is that mechanical stimulation of the motor activates local and global responses that trigger c-di-GMP signaling. The central hypothesis will be tested by experimentally characterizing motor mechanoreception and using high-throughput genetics to delineate the mechano-transduction pathways. These goals will utilize a combination of biophysical, imaging, molecular, and genomic tools. The expected outcome of this work is an improved understanding of how the flagellar motor of bacteria is involved in surface sensing. The long-term goal is to study how bacteria generate complex behaviors using simple molecular machinery. The training phase of this career development award outlines a comprehensive plan for the acquisition of technical and professional skills that will enable the PI’s transition into an independent research position. The successful completion of this project will provide a platform for future research aimed at revealing the molecular interactions and the underlying physical biology that enable complex bacterial behavior such as biofilm formation.

项目总结/文摘