The goals of the lipid mass spectrometry (MS) technological research and development program (TRD3) are to extend the study of ion chemistry and fragmentation mechanisms pioneered by M.L. Gross (Resource PI) and his staff specifically to biomedically important complex lipid molecules. Studies of lipid structures in TRD3 complement the biophysical studies in TRD1 by offering the opportunity to study protein interactions with lipids and membranes, including lipid-metabolizing enzymes. Lipid-protein and lipid-membrane interactions are relevant to the interactions of the signaling enzyme Group VIA PLA2 with membrane substrates, allosteric modifiers, and pharmacologic inhibitors (TRD1, C&S1, C&S2); to the recognition of lipid antigen-CD1 protein complexes by T cell receptors of Natural Killer T cells (DBP6); and to interactions of the Fatty Acid Synthase protein complex with subcellular membranes (DBP9, C&S3). TRD3 lipid MS technologies are integrated with TRD4 initiatives by providing the opportunity for complementary development of ESI-LIT-MSn with low energy collisionally activated dissociation (CAD) in parallel with MALDI-TOF-TOF-MS/MS with high energy CAD to provide overlapping but non-redundant structural information for classes of large stable biomolecules that are difficult to fragment under conditions of low energy CAD, such as glycan moieties of glycolipid antigens (DBP7), archaeal ether lipids useful in immunoadjuvant preparation (C&S4), and mycolic acids (DBP6, DBP7) that are potential diagnostic biomarkers. A unique feature of the WU Biomedical MS Resource is that MS technologies and expertise co-exist to conduct state-of-the-art studies of widely diverse molecular classes and create the opportunity to study interactions of molecular species as diverse as complex lipids and proteins.

Public Health Relevance

-Public Health Relevance. The Washington University Biomedical Mass Spectrometry Resource has a longstanding history as an active and productive citizen in the NIH Biotechnology 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 #
9199436
Study Section
Special Emphasis Panel (ZRG1-IMST-B)
Project Start
Project End
Budget Start
2017-01-01
Budget End
2017-12-31
Support Year
40
Fiscal Year
2017
Total Cost
$100,110
Indirect Cost
$34,464
Name
Washington University
Department
Type
Domestic Higher Education
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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
Illes-Toth, Eva; Rempel, Don L; Gross, Michael L (2018) Pulsed Hydrogen-Deuterium Exchange Illuminates the Aggregation Kinetics of ?-Synuclein, the Causative Agent for Parkinson's Disease. ACS Chem Neurosci 9:1469-1476
Johnston, Adam B; Hilton, Denise M; McConnell, Patrick et al. (2018) A novel mode of capping protein-regulation by twinfilin. Elife 7:
Ikon, Nikita; Hsu, Fong-Fu; Shearer, Jennifer et al. (2018) Evaluation of cardiolipin nanodisks as lipid replacement therapy for Barth syndrome J Biomed Res 32:107-112
Schweitzer, George G; Collier, Sara L; Chen, Zhouji et al. (2018) Loss of lipin 1-mediated phosphatidic acid phosphohydrolase activity in muscle leads to skeletal myopathy in mice. FASEB J :fj201800361R

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