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 #
5P01GM051487-18
Application #
8486439
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
2013-06-01
Budget End
2014-05-31
Support Year
18
Fiscal Year
2013
Total Cost
$1,753,099
Indirect Cost
$751,761
Name
Lawrence Berkeley National Laboratory
Department
Biochemistry
Type
Organized Research Units
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720
Zhang, Rui; LaFrance, Benjamin; Nogales, Eva (2018) Separating the effects of nucleotide and EB binding on microtubule structure. Proc Natl Acad Sci U S A 115:E6191-E6200
Nogales, Eva (2018) Cytoskeleton in high resolution. Nat Rev Mol Cell Biol 19:142
Downing, Kenneth H; Glaeser, Robert M (2018) Estimating the effect of finite depth of field in single-particle cryo-EM. Ultramicroscopy 184:94-99
Nogales, Eva (2018) Cryo-EM. Curr Biol 28:R1127-R1128
Sazzed, Salim; Song, Junha; Kovacs, Julio A et al. (2018) Tracing Actin Filament Bundles in Three-Dimensional Electron Tomography Density Maps of Hair Cell Stereocilia. Molecules 23:
Kamennaya, Nina A; Zemla, Marcin; Mahoney, Laura et al. (2018) High pCO2-induced exopolysaccharide-rich ballasted aggregates of planktonic cyanobacteria could explain Paleoproterozoic carbon burial. Nat Commun 9:2116
Howes, Stuart C; Geyer, Elisabeth A; LaFrance, Benjamin et al. (2018) Structural and functional differences between porcine brain and budding yeast microtubules. Cell Cycle 17:278-287
Glaeser, Robert M (2018) PROTEINS, INTERFACES, AND CRYO-EM GRIDS. Curr Opin Colloid Interface Sci 34:1-8
Kellogg, Elizabeth H; Hejab, Nisreen M A; Poepsel, Simon et al. (2018) Near-atomic model of microtubule-tau interactions. Science 360:1242-1246
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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