Abstract

This project is innovative in both the questions to be addressed and many of the tools to be employed. Mechanotransduction by integrin-dependent adhesions is a major area of current interest but detailed molecular mechanisms are pooriy understood. What stands out compared to ether studies is that we propose to study these phenomena in the context of high resolution analysis of cytoskeletal and receptor dynamics. This combination is highly nevel and offers major opportunities for deeper molecular understanding of what is, in essence, a dynamic phenomenon. Additionally, numerous technical innovations will be combined in this study. These include analysis of mutants of integrins and cytoskeletal proteins, a state of the art, high resolution EM technique, novel materials, nevel biosensors, and nevel imaging and data analysis methods. The application therefore contains mulfiple innovative aspects that take it far beyond current work.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
1P01GM098412-01
Application #
8234227
Study Section
Special Emphasis Panel (ZRG1-CB-D (40))
Project Start
2011-09-30
Project End
2016-08-31
Budget Start
2011-09-30
Budget End
2012-08-31
Support Year
1
Fiscal Year
2011
Total Cost
$274,590
Indirect Cost

  Institution

Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Chen, Zhenguo; Sun, Lei; Zhang, Zhihong et al. (2017) Cryo-EM structure of the bacteriophage T4 isometric head at 3.3-Å resolution and its relevance to the assembly of icosahedral viruses. Proc Natl Acad Sci U S A 114:E8184-E8193
Bachir, Alexia I; Horwitz, Alan Rick; Nelson, W James et al. (2017) Actin-Based Adhesion Modules Mediate Cell Interactions with the Extracellular Matrix and Neighboring Cells. Cold Spring Harb Perspect Biol 9:
Anderson, Karen L; Page, Christopher; Swift, Mark F et al. (2017) Nano-scale actin-network characterization of fibroblast cells lacking functional Arp2/3 complex. J Struct Biol 197:312-321
Xu, Xiao-Ping; Kim, Eldar; Swift, Mark et al. (2016) Three-Dimensional Structures of Full-Length, Membrane-Embedded Human ?(IIb)?(3) Integrin Complexes. Biophys J 110:798-809
Brenner, Michael D; Zhou, Ruobo; Conway, Daniel E et al. (2016) Spider Silk Peptide Is a Compact, Linear Nanospring Ideal for Intracellular Tension Sensing. Nano Lett 16:2096-102
Kumar, Abhishek; Ouyang, Mingxing; Van den Dries, Koen et al. (2016) Talin tension sensor reveals novel features of focal adhesion force transmission and mechanosensitivity. J Cell Biol 213:371-83
Vertelov, Grigory; Gutierrez, Edgar; Lee, Sin-Ae et al. (2016) Rigidity of silicone substrates controls cell spreading and stem cell differentiation. Sci Rep 6:33411
Tee, Yee Han; Shemesh, Tom; Thiagarajan, Visalatchi et al. (2015) Cellular chirality arising from the self-organization of the actin cytoskeleton. Nat Cell Biol 17:445-57
Hassler, Justin R; Scheuner, Donalyn L; Wang, Shiyu et al. (2015) The IRE1?/XBP1s Pathway Is Essential for the Glucose Response and Protection of ? Cells. PLoS Biol 13:e1002277
Bober, Brian G; Gutierrez, Edgar; Plaxe, Steven et al. (2015) Combinatorial influences of paclitaxel and strain on axonal transport. Exp Neurol 271:358-67

Showing the most recent 10 out of 27 publications