Nanoscale soft x-ray tomography is a powerful new imaging technology for biomedical and translational research. This technique produces high spatial resolution, high-fidelity 3-Dimensional tomographic reconstructions of the specimen, and does so with unprecedented sample throughput. The work of this proposal will further enhance the applicability, usability and fidelity of soft x-ray tomography as a biomedical imaging technique, make it applicable to a greater range of specimen types, significantly increase spatial resolution, and extend the tools and options available for protein localization. We will continue development of our pioneering work on correlated cryogenic fluorescence microscopy. These efforts, and the planned instrumental and technological developments, will allow multi-modal imaging to be carried out on specimens containing endogenous or exogenous fluorescent labels. The end result will be a suite of imaging options that allow protein localization data to be optimally positioned within a 3-Dimensional reconstruction of the specimen. In soft x-ray tomography the image contrast is derived from the biochemical composition of the specimen. Apart from eliminating the need to fix and stain the specimen this results in each organelle having a signature linear x-ray absorption coefficient. This measurement can be used to identify and quantifiably characterize organelles within a specimen and between different specimens. This type of information, together with the location of specific molecules in the specimen is key to understanding the cellular effects of disease, identifying and validating drug targets, and determining modes of action of molecules with therapeutic potential.

Public Health Relevance

Technologies are being developed to visualize the effects of disease on cell structure and organization. This is important information in the identification and validation of targets for drug design, and for determining the mode of action of molecules with therapeutic potential. This technology can be applied to understanding the cellular effects of cancer, or infection, whether it be microbial, viral or parasitic in origin.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
8P41GM103445-08
Application #
8265636
Study Section
Special Emphasis Panel (ZRG1-BST-K (40))
Program Officer
Swain, Amy L
Project Start
2004-05-06
Project End
2015-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
8
Fiscal Year
2012
Total Cost
$926,240
Indirect Cost
$298,877
Name
University of California San Francisco
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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