This Program Project represents a coordinated and mutually supporting effort to pursue research in structural biology where electron diffraction and electron microscopy play a key role and to advance the technology that enables this research. Three projects within the Program represent applications of the methods of electron crystallography and microscopy, as well as of the instrumentation supported by the Program, to specific problems in structural biology. These applications focus on aspects of the eukaryotic cytoskeleton and include: (Project A) Studies of the structure of tubulin and its interactions with ligands and other proteins that affect the function of the microtubule cytoskeleton;(Project B) Studies of the apparatus in the inner ear that converts sound to nerve signals and controls sensitivity of hearing;(Project C) Studies of the proteins that connect microtubules to chromosomes and ensure proper chromosome segregation during cell division. Additional, separately funded research projects which rely to a smaller extent on equipment and facilities supported by the Program Project are also included as Associate member projects. The Administrative Core (Project D) maintains the major equipment, supports computer resources, continues our efforts to improve the quality and throughput of electron microscopy data, and provides a sense of intellectual community and common identity for all the participants in the Program Project.

Public Health Relevance

Our structural studies of several medically important protein complexes that play essential roles within the cell provide the basis for understanding their normal function as well as failures in these functions that are associated with disease and birth defects.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM051487-16
Application #
8119713
Study Section
Special Emphasis Panel (ZRG1-CB-B (40))
Program Officer
Flicker, Paula F
Project Start
1997-07-01
Project End
2015-05-31
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
16
Fiscal Year
2011
Total Cost
$1,816,425
Indirect Cost
Name
Lawrence Berkeley National Laboratory
Department
Biochemistry
Type
Organized Research Units
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720
Nogales, Eva; Kellogg, Elizabeth H (2017) Challenges and opportunities in the high-resolution cryo-EM visualization of microtubules and their binding partners. Curr Opin Struct Biol 46:65-70
Hurley, James H; Young, Lindsey N (2017) Mechanisms of Autophagy Initiation. Annu Rev Biochem 86:225-244
Han, Bong-Gyoon; Watson, Zoe; Cate, Jamie H D et al. (2017) Monolayer-crystal streptavidin support films provide an internal standard of cryo-EM image quality. J Struct Biol 200:307-313
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Howes, Stuart C; Geyer, Elisabeth A; LaFrance, Benjamin et al. (2017) Structural differences between yeast and mammalian microtubules revealed by cryo-EM. J Cell Biol 216:2669-2677
Jorgens, Danielle M; Inman, Jamie L; Wojcik, Michal et al. (2017) Deep nuclear invaginations are linked to cytoskeletal filaments - integrated bioimaging of epithelial cells in 3D culture. J Cell Sci 130:177-189
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Chiu, Wah; Downing, Kenneth H (2017) Editorial overview: Cryo Electron Microscopy: Exciting advances in CryoEM Herald a new era in structural biology. Curr Opin Struct Biol 46:iv-viii

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