The goal of Core K (Prenols and Other Lipids) is to provide comprehensive approaches to the isolation and identification of diverse prenols, cardiolipins and novel minor lipids in mouse macrophages and related sources under basal, stimulated or drug-treated conditions. The strategy will involve the quantification of known lipids, and the purification and structural characterization of novel minor lipids by state of the art ESI mass spectrometry and other structural methods. Core K will collaborate with other cores of the Consortium as they encounter new lipids in need of identification. Core K will work with the Chemistry Focus Area to ensure that novel structural proposals are validated by synthesis in a timely manner. In the coming grant period, Core K has the following specific aims, which are fully integrated with the rest of the Consortium:
Specific Aim 1. Employ lipidomics to advance mechanistic understanding of metabolism, especially as it relates to prenols, cardiolipins and novel minor lipids. In addition to the Consortium-related aims, several hypothesis-driven approaches are described for elucidating the biosynthesis and function the A/-acyl-phosphatidylserines, a novel family of lipids discovered during the last grant period.
Specific Aim 2 : Employ lipidomics to investigate macrophages and tissues under pathological conditions as disease models, with emphasis on prenols, cardiolipins and novel minor lipids. In addition to the Consortium-related aims, hypothesis-driven approaches are described for elucidating the biosynthesis and function of the dolichoic acids, new prenols discovered in brain neuromelanin granules.
Specific Aim 3 : Develop lipid networks and maps from lipidomics data analysis, with a focus on prenols, cardiolipins and novel minor lipids. In addition to the Consortium-related aims, Core K will provide annotated pathways for lipid categories in model systems, like E. coli and yeast, which are not the focus of LIPID MAPS, but which are invaluable for uncovering new mechanisms of lipid biosynthesis and genetics. A comprehensive knowledge of the structure and function of lipids is crucial for understanding the mechanisms of important disease processes, such as atherosclerosis, inflammation and diabetes. The quantitative measurement of lipid levels enabled by mass spectrometry also facilitates the evaluation of the therapeutic actions of commonly used drugs, such as the cholesterol lowering or insulin sensitizing agents.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54GM069338-10
Application #
8382529
Study Section
Special Emphasis Panel (ZGM1-CBB-5)
Project Start
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
10
Fiscal Year
2012
Total Cost
$447,088
Indirect Cost
$90,414
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Young, Hayley E; Zhao, Jinshi; Barker, Jeffrey R et al. (2016) Discovery of the Elusive UDP-Diacylglucosamine Hydrolase in the Lipid A Biosynthetic Pathway in Chlamydia trachomatis. MBio 7:e00090
Tribble, Emily K; Ivanova, Pavlina T; Grabon, Aby et al. (2016) Quantitative profiling of the endonuclear glycerophospholipidome of murine embryonic fibroblasts. J Lipid Res 57:1492-506
Bonnington, Katherine E; Kuehn, Meta J (2016) Outer Membrane Vesicle Production Facilitates LPS Remodeling and Outer Membrane Maintenance in Salmonella during Environmental Transitions. MBio 7:
Li, Chijun; Tan, Brandon K; Zhao, Jinshi et al. (2016) In Vivo and in Vitro Synthesis of Phosphatidylglycerol by an Escherichia coli Cardiolipin Synthase. J Biol Chem 291:25144-25153
Guan, Ziqiang; Chen, Lingli; Gerritsen, Jacoline et al. (2016) The cellular lipids of Romboutsia. Biochim Biophys Acta 1861:1076-82
Dennis, Edward A (2016) Liberating Chiral Lipid Mediators, Inflammatory Enzymes, and LIPID MAPS from Biological Grease. J Biol Chem 291:24431-24448
Guan, Ziqiang; Delago, Antonia; Nußbaum, Phillip et al. (2016) N-glycosylation in the thermoacidophilic archaeon Sulfolobus acidocaldarius involves a short dolichol pyrophosphate carrier. FEBS Lett 590:3168-78
Gupta, Shakti; Kihara, Yasuyuki; Maurya, Mano R et al. (2016) Computational Modeling of Competitive Metabolism between ω3- and ω6-Polyunsaturated Fatty Acids in Inflammatory Macrophages. J Phys Chem B 120:8346-53
Dennis, Edward A; Norris, Paul C (2015) Eicosanoid storm in infection and inflammation. Nat Rev Immunol 15:511-23
Crotti, Andrea; Glass, Christopher K (2015) The choreography of neuroinflammation in Huntington's disease. Trends Immunol 36:364-73

Showing the most recent 10 out of 374 publications