As fundamental research in biology increasingly focuses on events occurring at the macromolecular level, structural studies at molecular and supramolecular levels become especially important. Electron microscopy provides high resolution structural information, which exceeds in resolution and a span of applications even most advanced light microscopic approaches. The major limitation of electron microscopy, its applicability only to "dead" samples, can be partially overcome by correlating the structural organization of a fixed sample with its dynamic behavior recorded prior to fixation using light microscopic approaches. This electron microscopy core unit will supply electron microscopy services for the program including sample preparation and analysis by a variety of electron microscopy techniques. The core will also develop advanced techniques in correlative light and electron microscopy specifically suited for the investigation of molecular motors and vesicle trafficking in cells and in cell-free motility systems. These new techniques will be also made available to the core users.

Public Health Relevance

Electron microscopy is a unique tool to get insight into fine structural organization of tissues, cells, and molecules. Such structural information paves a road toward understanding of complex biological processes, without which it is not possible to fight a disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM087253-10
Application #
8507754
Study Section
Special Emphasis Panel (ZRG1-CB-P)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
10
Fiscal Year
2013
Total Cost
$122,080
Indirect Cost
$44,429
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Hendricks, Adam G; Goldman, Yale E; Holzbaur, Erika L F (2014) Reconstituting the motility of isolated intracellular cargoes. Methods Enzymol 540:249-62
Zajac, Allison L; Goldman, Yale E; Holzbaur, Erika L F et al. (2013) Local cytoskeletal and organelle interactions impact molecular-motor- driven early endosomal trafficking. Curr Biol 23:1173-80
Greenberg, Michael J; Ostap, E Michael (2013) Regulation and control of myosin-I by the motor and light chain-binding domains. Trends Cell Biol 23:81-9
Hendricks, Adam G; Lazarus, Jacob E; Perlson, Eran et al. (2012) Dynein tethers and stabilizes dynamic microtubule plus ends. Curr Biol 22:632-7
Wang, Yu-Hsiu; Collins, Agnieszka; Guo, Lin et al. (2012) Divalent cation-induced cluster formation by polyphosphoinositides in model membranes. J Am Chem Soc 134:3387-95
Sun, Yujie; Goldman, Yale E (2011) Lever-arm mechanics of processive myosins. Biophys J 101:1-11
Collins, Agnieszka; Warrington, Anthony; Taylor, Kenneth A et al. (2011) Structural organization of the actin cytoskeleton at sites of clathrin-mediated endocytosis. Curr Biol 21:1167-75
Schroeder 3rd, Harry W; Mitchell, Chris; Shuman, Henry et al. (2010) Motor number controls cargo switching at actin-microtubule intersections in vitro. Curr Biol 20:687-96
Arsenault, Mark E; Purohit, Prashant K; Goldman, Yale E et al. (2010) Comparison of Brownian-dynamics-based estimates of polymer tension with direct force measurements. Phys Rev E Stat Nonlin Soft Matter Phys 82:051923
Holzbaur, Erika L F; Goldman, Yale E (2010) Coordination of molecular motors: from in vitro assays to intracellular dynamics. Curr Opin Cell Biol 22:4-13