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 #
5P41GM103422-39
Application #
9044798
Study Section
Special Emphasis Panel (ZRG1-IMST-B)
Project Start
Project End
Budget Start
2016-01-01
Budget End
2016-12-31
Support Year
39
Fiscal Year
2016
Total Cost
$100,110
Indirect Cost
$34,464
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Henson, William R; Hsu, Fong-Fu; Dantas, Gautam et al. (2018) Lipid metabolism of phenol-tolerant Rhodococcus opacus strains for lignin bioconversion. Biotechnol Biofuels 11:339
Lucey, Brendan P; Hicks, Terry J; McLeland, Jennifer S et al. (2018) Effect of sleep on overnight cerebrospinal fluid amyloid ? kinetics. Ann Neurol 83:197-204
Johnson, Britney; McConnell, Patrick; Kozlov, Alex G et al. (2018) Allosteric Coupling of CARMIL and V-1 Binding to Capping Protein Revealed by Hydrogen-Deuterium Exchange. Cell Rep 23:2795-2804
Shu, Longfei; Zhang, Bojie; Queller, David C et al. (2018) Burkholderia bacteria use chemotaxis to find social amoeba Dictyostelium discoideum hosts. ISME J 12:1977-1993
Zayed, Mohamed A; Hsu, Fong-Fu; Patterson, Bruce W et al. (2018) Diabetes adversely affects phospholipid profiles in human carotid artery endarterectomy plaques. J Lipid Res 59:730-738
Xu, Wei; Mukherjee, Sumit; Ning, Yu et al. (2018) Cyclopropane fatty acid synthesis affects cell shape and acid resistance in Leishmania mexicana. Int J Parasitol 48:245-256
Luo, Zonghua; Rosenberg, Adam J; Liu, Hui et al. (2018) Syntheses and in vitro evaluation of new S1PR1 compounds and initial evaluation of a lead F-18 radiotracer in rodents. Eur J Med Chem 150:796-808
Rajagopal, Rithwick; Zhang, Sheng; Wei, Xiaochao et al. (2018) Retinal de novo lipogenesis coordinates neurotrophic signaling to maintain vision. JCI Insight 3:
van Vliet, Stephan; Smith, Gordon I; Porter, Lane et al. (2018) The muscle anabolic effect of protein ingestion during a hyperinsulinaemic euglycaemic clamp in middle-aged women is not caused by leucine alone. J Physiol 596:4681-4692
Keul, Nicholas D; Oruganty, Krishnadev; Schaper Bergman, Elizabeth T et al. (2018) The entropic force generated by intrinsically disordered segments tunes protein function. Nature 563:584-588

Showing the most recent 10 out of 323 publications