The National Center for Microscopy and Imaging Research (NCMIR) was established to develop computeraided advanced microscopy for acquisition of structural and functional data in the dimensional range of 1 nm to 100 ?mu?m, a range encompassing macromolecules, subcellular structures and cells. With novel specimen staining methods, imaging instruments and computational capabilities, researchers are addressing the next great biological challenges in the post-genomic age by situating proteins and macromolecular complexes in their cellular and tissue environments. Resource instruments include intermediate high voltage transmission electron microscopes (IVEMs) and high-speed large-format laser-scanning light microscopes specially modified for """"""""mesoscale"""""""" biological microscopy. Our collaboration, service, training and dissemination programs expand the development and use of these technologies to maximize their value to the biomedical community. In this application, NCMIR continues to develop novel methods for imaging biological systems across scales, building upon our successes during the previous funding period and expanding into new areas of technology development. Core technology projects are proposed to develop new staining methods, imaging modes and computational tools for correlated 3D imaging using unique optical and higher voltage electron microscopes. Core research is driven by collaboration with leading scientists in the US and around the world who are addressing key questions in basic cell- and neurobiology and conducting translational research in neurodegenerative disease, stroke, cancer, heart failure and infectious disease, to name a few. A unique focus of this resource continues to be the utilization of advanced computational infrastructure to allow remote access to instruments, data and computational resources and to foster collaborations among widely distributed scientists. These new technologies were substantially enhanced over the preceding funding period and will be deployed within our resource to support core and collaborative research. Through this infrastructure, we provide researchers greater access to the Resource through web-based remote control systems for the optical and higher voltage electron microscopes, processing workflows for wide field fluorescence microscopy and electron tomography, and interfaces for computational grids and distributed databases via high-speed networks. In this proposal, we expand these activities to include web-based informatics tools for managing, searching, mining and sharing large multidimensional data sets. These data are shared with the public through the Cell Centered Database, a database for 2D, 3D and 4D microscopy data.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
8P41GM103412-24
Application #
8254415
Study Section
Special Emphasis Panel (ZRG1-BST-R (40))
Program Officer
Swain, Amy L
Project Start
1997-05-15
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
24
Fiscal Year
2012
Total Cost
$2,368,554
Indirect Cost
$799,189
Name
University of California San Diego
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Phan, S├ębastien; Boassa, Daniela; Nguyen, Phuong et al. (2017) 3D reconstruction of biological structures: automated procedures for alignment and reconstruction of multiple tilt series in electron tomography. Adv Struct Chem Imaging 2:8
Rodriguez, Erik A; Campbell, Robert E; Lin, John Y et al. (2017) The Growing and Glowing Toolbox of Fluorescent and Photoactive Proteins. Trends Biochem Sci 42:111-129
de Vivo, Luisa; Bellesi, Michele; Marshall, William et al. (2017) Ultrastructural evidence for synaptic scaling across the wake/sleep cycle. Science 355:507-510
Cao, Mian; Wu, Yumei; Ashrafi, Ghazaleh et al. (2017) Parkinson Sac Domain Mutation in Synaptojanin 1 Impairs Clathrin Uncoating at Synapses and Triggers Dystrophic Changes in Dopaminergic Axons. Neuron 93:882-896.e5
Zifan, Ali; Kumar, Dushyant; Cheng, Leo K et al. (2017) Three-Dimensional Myoarchitecture of the Lower Esophageal Sphincter and Esophageal Hiatus Using Optical Sectioning Microscopy. Sci Rep 7:13188
Wan, Xiaohua; Katchalski, Tsvi; Churas, Christopher et al. (2017) Electron tomography simulator with realistic 3D phantom for evaluation of acquisition, alignment and reconstruction methods. J Struct Biol 198:103-115
Petersen, Mark A; Ryu, Jae Kyu; Chang, Kae-Jiun et al. (2017) Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage. Neuron 96:1003-1012.e7
Jimenez-Caliani, Antonio J; Pillich, Rudolf; Yang, Wendy et al. (2017) ?E-Catenin Is a Positive Regulator of Pancreatic Islet Cell Lineage Differentiation. Cell Rep 20:1295-1306
Gillies, Allison R; Chapman, Mark A; Bushong, Eric A et al. (2017) High resolution three-dimensional reconstruction of fibrotic skeletal muscle extracellular matrix. J Physiol 595:1159-1171
Ilouz, Ronit; Lev-Ram, Varda; Bushong, Eric A et al. (2017) Isoform-specific subcellular localization and function of protein kinase A identified by mosaic imaging of mouse brain. Elife 6:

Showing the most recent 10 out of 101 publications