PRENOLS AND OTHER LIPIDS

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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.