: New microscopy technologies will be developed and made available to biomedical researchers to bridge understanding of biological systems across gross anatomical and molecular scales. Project technology development efforts take on two important challenges: addressing the mesoscale range - from a few nanometers to 100 microns, required to see complexes in the context of cellular aggregates in tissues - and developing/advancing capabilities to enable multimodal imaging, that is, correlated imaging across a range of instruments (and their varying capabilities), to allow combining of data from the same specimens, providing new understanding of processes related to disease mechanisms. To achieve these two goals, activities will be in four related technology thrusts: probe development in Core 1, specimen development in Core 2, imaging instrument development in Core 3, and development of software tools to refine, integrate, analyze, and share microscopy data in Core 4. Core 1 will focus on labeling strategies for various new genetic or enzymatic probes. Core 2 will refine specimen-preparation protocols and materials to provide more suitable samples for examination. The combined outcome of these first two cores will be to streamline imaging using correlated microscopy by creating specimens better suited to a range of imaging modalities and enhancing the palette of in-situ markers to facilitate tracking areas of interest in related images and achieve their co-registration. Tracking methods, to be developed by activities of Cores 2 and 3, will be used to connect data in databases using new data analysis tools of Core 4, developing new tools for segmentation and annotation of images. Core 3 advances the imaging capabilities of multiple microscope types to deliver information not only with greater sensitivity and accuracy but more rapidly and seamlessly across scales. The work of all Cores, but especially the instrument development Core 3, will enable more sophisticated use of a next generation microscopes and their application to important biomedical research challenges. Core 4 develops software tools and infrastructure to refine, integrate, quantify, interpret, and add value to image data derived from the new instruments. The coordinated work among the four cores and collaborator projects will enable biomedical researchers to image wider, see deeper, increase contrast and differentiate complex structures, and observe complex phenomena at higher resolution and at faster time scales. Thus we will propel biomedical research requiring traversal of now difficult to navigate spatial scales, thereby facilitating new understanding of the molecular mechanisms underlying disease processes.

Public Health Relevance

Projects facilitated by the new technological resources to be developed involve neurodegenerative disease, cancer, infectious disease, heart disease, diabetes and virtually all aspects of biomedical research.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
2P41GM103412-26
Application #
8608238
Study Section
Special Emphasis Panel (ZRG1-BST-H (40))
Program Officer
Swain, Amy L
Project Start
1997-05-15
Project End
2019-03-31
Budget Start
2014-05-01
Budget End
2015-03-31
Support Year
26
Fiscal Year
2014
Total Cost
$2,052,006
Indirect Cost
$728,131
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
Shim, Myoung Sup; Kim, Keun-Young; Noh, Mark et al. (2018) Optineurin E50K triggers BDNF deficiency-mediated mitochondrial dysfunction in retinal photoreceptor cell line. Biochem Biophys Res Commun 503:2690-2697
Tsang, Tin Ki; Bushong, Eric A; Boassa, Daniela et al. (2018) High-quality ultrastructural preservation using cryofixation for 3D electron microscopy of genetically labeled tissues. Elife 7:
Katchalski, Tsvi; Case, Tom; Kim, Keun-Young et al. (2018) Iron-specific Signal Separation from within Heavy Metal Stained Biological Samples Using X-Ray Microtomography with Polychromatic Source and Energy-Integrating Detectors. Sci Rep 8:7553
Shim, Myoung Sup; Kim, Keun-Young; Bu, Jung Hyun et al. (2018) Elevated intracellular cAMP exacerbates vulnerability to oxidative stress in optic nerve head astrocytes. Cell Death Dis 9:285
Liu, Jenney; Lee, Icksoo; Feng, Han-Zhong et al. (2018) Aerobic Exercise Preconception and During Pregnancy Enhances Oxidative Capacity in the Hindlimb Muscles of Mice Offspring. J Strength Cond Res 32:1391-1403
Deerinck, T J; Shone, T M; Bushong, E A et al. (2018) High-performance serial block-face SEM of nonconductive biological samples enabled by focal gas injection-based charge compensation. J Microsc 270:142-149
Lee, Jennifer K; Enciso, Germán A; Boassa, Daniela et al. (2018) Replication-dependent size reduction precedes differentiation in Chlamydia trachomatis. Nat Commun 9:45
McGlynn, Shawn E; Chadwick, Grayson L; O'Neill, Ariel et al. (2018) Subgroup characteristics of marine methane-oxidizing ANME-2 archaea and their syntrophic partners revealed by integrated multimodal analytical microscopy. Appl Environ Microbiol :
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:
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

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