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.
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.
|Yue, Xuyi; Jin, Hongjun; Luo, Zonghua et al. (2017) Chiral resolution of serial potent and selective ?1 ligands and biological evaluation of (-)-[18F]TZ3108 in rodent and the nonhuman primate brain. Bioorg Med Chem 25:1533-1542|
|Wallen, Jamie R; Zhang, Hao; Weis, Caroline et al. (2017) Hybrid Methods Reveal Multiple Flexibly Linked DNA Polymerases within the Bacteriophage T7 Replisome. Structure 25:157-166|
|Domingo-Gonzalez, Racquel; Das, Shibali; Griffiths, Kristin L et al. (2017) Interleukin-17 limits hypoxia-inducible factor 1? and development of hypoxic granulomas during tuberculosis. JCI Insight 2:|
|Reeds, Dominic N; Pietka, Terri A; Yarasheski, Kevin E et al. (2017) HIV infection does not prevent the metabolic benefits of diet-induced weight loss in women with obesity. Obesity (Silver Spring) 25:682-688|
|Frieden, Carl; Wang, Hanliu; Ho, Chris M W (2017) A mechanism for lipid binding to apoE and the role of intrinsically disordered regions coupled to domain-domain interactions. Proc Natl Acad Sci U S A 114:6292-6297|
|Lu, Yue; Liu, Haijun; Saer, Rafael G et al. (2017) Native Mass Spectrometry Analysis of Oligomerization States of Fluorescence Recovery Protein and Orange Carotenoid Protein: Two Proteins Involved in the Cyanobacterial Photoprotection Cycle. Biochemistry 56:160-166|
|Wang, Hanliu; Shu, Qin; Frieden, Carl et al. (2017) Deamidation Slows Curli Amyloid-Protein Aggregation. Biochemistry 56:2865-2872|
|Ohlemacher, Shannon I; Giblin, Daryl E; d'Avignon, D André et al. (2017) Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria. J Clin Invest 127:4018-4030|
|Zhang, Hao; Harrington, Lucas B; Lu, Yue et al. (2017) Native Mass Spectrometry Characterizes the Photosynthetic Reaction Center Complex from the Purple Bacterium Rhodobacter sphaeroides. J Am Soc Mass Spectrom 28:87-95|
|Wang, Hanliu; Shu, Qin; Rempel, Don L et al. (2017) Understanding Curli Amyloid-Protein Aggregation by Hydrogen-Deuterium Exchange and Mass Spectrometry. Int J Mass Spectrom 420:16-23|
Showing the most recent 10 out of 287 publications