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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Program Projects (P01)
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Special Emphasis Panel (ZRG1-CB-B (40))
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Flicker, Paula F
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Lawrence Berkeley National Laboratory
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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
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
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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
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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