PI: Daniel Fletcher, Ph.D. NIH R01 application, PA-18-484 Project Title: Mechanical regulation of acting binding proteins Project Period: 07/01/2019 ? 06/30/2024 The actin cytoskeleton consists of spatially organized structures of filaments that are architecturally distinct and formed from over 300 different actin-binding proteins. One of the key roles of actin networks in cells is to generate, transmit, and resist physical forces, but whether the forces carried by actin filaments influence the binding of actin-binding proteins is not well understood. This proposal will investigate the ability of tandem calponin-homology domains (CH1-CH2) to bind actin filaments in a tension-dependent manner, and it will explore the functional impact of tension-dependent binding through a set of in vitro experiments measuring the mechanical properties of actin gels with tension-dependent crosslinkers and live cells experiments quantifying the effect of tension-dependent signaling and cytoskeletal organization on crawling motility. The outcome of this work will be a new understanding of how force can organize actin networks and influence the function of both healthy and diseased cells.

Public Health Relevance

PI: Daniel Fletcher, Ph.D. NIH R01 application, PA-18-484 Project Title: Mechanical regulation of acting binding proteins Project Period: 07/01/2019 ? 06/30/2024 A primary role of the actin cytoskeleton is to generates and transmit forces through cells, but it is unclear whether forces on filaments could affect the localization of the myriad actin-binding proteins in cells. Here we test the ability of the most common actin-binding domain to bind actin filaments in a tension-dependent manner and explore the effects of tension-dependent actin-binding proteins on cell migration.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM134137-01
Application #
9803020
Study Section
Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section (NCSD)
Program Officer
Xu, Jianhua
Project Start
2019-07-25
Project End
2023-04-30
Budget Start
2019-07-25
Budget End
2020-04-30
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94710