ARRA: Role of Lipid Phosphatases in Cholesterol and Triglyceride Synthesis

This application requests funds for an administrative supplement to R01GM50388-16 “Role of Lipid Phosphatases in Cholesterol and Triglyceride Synthesis”. The broad goal of this ongoing research program is to identify and study the regulation and functions of key enzymes that play central roles in lipid metabolism and lipid signaling. Abberant or excessive production and storage of triglycerides and cholesterol forms the basis for a set of interrelated metabolic diseases including diet induced obesity and its complications of diabetes and cardiovascular disease. This award supports efforts to define roles for newly identified lipid phosphatase enzymes with critical roles these synthetic pathways. A major focus of the research is on manipulating expression levels of these enzymes in cell-based or animal models. Monitoring global changes in lipid metabolism mandates the use of newly developed analytical approaches using tandem liquid chromatography and multi- dimensional mass spectrometry. Using funds provided by a previously awarded NCRR Shared instrumentation grant (1S10RR024598-01, Andrew J. Morris, PI) we recently aquired an Applied Biosystems (ABI)/MDS Sciex 4000 Q-Trap hybrid triple quadrupole linear ion trap mass spectrometer. We are requesting funds to upgrade the instrument with an Advion Nanomate Triversa chip infusion system and an ABI Nanospray II ion source. This upgrade will allow us to use our instrument for lipid profiling studies by automated nanospray electrospray ionization mass spectrometry. Acquisition of this upgraded instrumentation will greatly accelerate the pace of our research, particularly since we have recently generated mice with targeted inactivation of some of the genes of interest. Because our growing lipid mass spectrometry capabilities are used by other NIH-supported researchers the impact of this upgraded instrumentation will be broad. Most importantly, the instrumentation we request is manufactured, marketed and supported by domestic companies (Advion Biosciences, Ithaca, NY and Applied Biosystems, Foster City, CA) so clearly this request will result in broad economic benefits consistent with the goals of the American Recovery and Reinvestment Act.