The Washington University NIGMS Biomedical Resource proposes to continue its 37 years of support for biomedical research through the development of technology based on mass spectrometry (MS). The Resource will pursue this in three areas: 1) The characterization of complex lipids and lipid biosynthesis with a focus on a) pathogenic microorganisms like trypanosomes and mycobacteria and the biosynthetic pathways that offer targets for therapy, b) the characterization of lipid antigens, and c) lipid mediators o fatty acid synthase; 2) The establishment of a biophysics center that offers MS-based tools to probe protein dynamics, protein interactions, protein complex stoichiometry and structure, and membrane proteins using a) hydrogen deuterium exchange MS, b) fast photochemical oxidation of proteins, c) top-down analysis of proteins, and d) crosslinking methods for complexes; and 3) the extension of high energy collisional activation methods for the study of complex lipids and large peptides, especially those predicted from genomic data. This technology development will be driven by nearly three dozen collaborative efforts that are broad in scientific and geographic scope and focused on the study of human health and disease. The technology will be made available to other collaborators through our extensive dissemination and training efforts.

Public Health Relevance

The Washington University Biomedical Mass Spectrometry Resource has a longstanding history as an active and productive citizen in the NIH Biomedical Technology Research Resources community. We propose to extend our mission by advancing mass spectrometry technology, development, and research, applying these discoveries to answer critical biomedical research questions, and training the next generation of researchers, towards the ultimate goal of improving public health.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
5P41GM103422-40
Application #
9199426
Study Section
Special Emphasis Panel (ZRG1-IMST-B (40)P)
Program Officer
Edmonds, Charles G
Project Start
1997-08-01
Project End
2019-12-31
Budget Start
2017-01-01
Budget End
2017-12-31
Support Year
40
Fiscal Year
2017
Total Cost
$1,181,756
Indirect Cost
$406,834
Name
Washington University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Zhang, Bojie; Cheng, Ming; Rempel, Don et al. (2018) Implementing fast photochemical oxidation of proteins (FPOP) as a footprinting approach to solve diverse problems in structural biology. Methods 144:94-103
Su, Zhaoming; Wu, Chao; Shi, Liuqing et al. (2018) Electron Cryo-microscopy Structure of Ebola Virus Nucleoprotein Reveals a Mechanism for Nucleocapsid-like Assembly. Cell 172:966-978.e12
Zhang, Mengru Mira; Rempel, Don L; Gross, Michael L (2018) A Fast Photochemical Oxidation of Proteins (FPOP) platform for free-radical reactions: the carbonate radical anion with peptides and proteins. Free Radic Biol Med 131:126-132
Shen, G; Li, S; Cui, W et al. (2018) Stabilization of warfarin-binding pocket of VKORC1 and VKORL1 by a peripheral region determines their different sensitivity to warfarin inhibition. J Thromb Haemost 16:1164-1175
Lu, Yue; Goodson, Carrie; Blankenship, Robert E et al. (2018) Primary and Higher Order Structure of the Reaction Center from the Purple Phototrophic Bacterium Blastochloris viridis: A Test for Native Mass Spectrometry. J Proteome Res 17:1615-1623
Fernandez, Estefania; Kose, Nurgun; Edeling, Melissa A et al. (2018) Mouse and Human Monoclonal Antibodies Protect against Infection by Multiple Genotypes of Japanese Encephalitis Virus. MBio 9:
Johnson, Britney; VanBlargan, Laura A; Xu, Wei et al. (2018) Human IFIT3 Modulates IFIT1 RNA Binding Specificity and Protein Stability. Immunity 48:487-499.e5
Girard, T J; Grunz, K; Lasky, N M et al. (2018) Re-evaluation of mouse tissue factor pathway inhibitor and comparison of mouse and human tissue factor pathway inhibitor physiology. J Thromb Haemost 16:2246-2257
Hsu, Fong-Fu (2018) Mass spectrometry-based shotgun lipidomics - a critical review from the technical point of view. Anal Bioanal Chem 410:6387-6409
Hung, Putzer J; Johnson, Britney; Chen, Bo-Ruei et al. (2018) MRI Is a DNA Damage Response Adaptor during Classical Non-homologous End Joining. Mol Cell 71:332-342.e8

Showing the most recent 10 out of 323 publications