Core B ? Molecular Biology and Lipidomics provides multiple essential services to every investigator working on this Program Project Grant. These services include routine experimental procedures as well as unique assays that provide unparalleled and comprehensive molecular insight into lipid metabolism. The core is directed by Dr. David W. Russell, who has served as its Principal Investigator for the past 30 years. Routine services include protein gel electrophoresis and immunoblotting; DNA sequencing of wild-type and mutant cDNAs and plasmid constructs; RNAseq assays to assess the transcriptomes of cells and tissues; quantitative PCR assays to measure mRNA levels expressed from hundreds of mouse, human, and hamster genes; the design and ordering of custom oligonucleotide probes and primers; the preparation of genomic and plasmid DNAs for experimentation and storage; and the assessment of physiological parameters (oxygen consumption, carbon dioxide production, hemodynamic parameters, weight gain and loss, activity, etc.) in living animals. Unique assays developed through the auspices of this Program Project include mass spectrometry- based quantification of individual lipid species including sterols, oxysterols, ceramides, steroids, bile acids, and fatty acids; lipidomic profiling that yields qualitative to semi-quantitative assessments of thousands of lipid molecular species; and flux measurements that quantify the flow of metabolites through a designated biosynthetic or catabolic pathway in cultured cells and living animals. The extensive and expensive equipment needed to provide these services, including multiple mass spectrometers, liquid-handling robots, metabolic cages, freezers, real-time PCR machines, and routine and next-generation DNA sequencers, is provided solely by the institution and represents a substantial cost-sharing investment. The services provided by this Core play a major role in every specific aim in this Program Project and in every publication that arises from the completed research. C/PPG 2015 ? Core B ? Project Summary

Public Health Relevance

The successful execution and completion of all four Research Projects in this Program Project Grant depend on the efficient and smooth operation of Core B?Molecular Biology and Lipidomics. This Core provides molecular biology assays (DNA sequencing, RNAseq, quantitative PCR, design and ordering of custom oligonucleotide probes and primers, etc.), lipidomic analysis (mass spectrometry-based quantification of individual lipid species), and assessment of special physiological parameters (oxygen consumption, carbon dioxide production, etc.). This Core is directed by David W. Russell, Ph.D., who has been its Principal Investigator for the past 30 years, and its day-to-day operation is carried out by several experienced technicians, one of whom (Jeff Cormier) has worked in this Core for the past 25 years. C/PPG 2015 - Core B - 3-Sentence Narrative

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Liu, Lijuan
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University of Texas Sw Medical Center Dallas
United States
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Mitsche, Matthew A; Hobbs, Helen H; Cohen, Jonathan C (2018) Patatin-like phospholipase domain-containing protein 3 promotes transfer of essential fatty acids from triglycerides to phospholipids in hepatic lipid droplets. J Biol Chem 293:6958-6968
Banfi, Serena; Gusarova, Viktoria; Gromada, Jesper et al. (2018) Increased thermogenesis by a noncanonical pathway in ANGPTL3/8-deficient mice. Proc Natl Acad Sci U S A 115:E1249-E1258
Fine, Michael; Schmiege, Philip; Li, Xiaochun (2018) Structural basis for PtdInsP2-mediated human TRPML1 regulation. Nat Commun 9:4192
Linden, Albert G; Li, Shili; Choi, Hwa Y et al. (2018) Interplay between ChREBP and SREBP-1c coordinates postprandial glycolysis and lipogenesis in livers of mice. J Lipid Res 59:475-487
Johnson, Brittany M; DeBose-Boyd, Russell A (2018) Underlying mechanisms for sterol-induced ubiquitination and ER-associated degradation of HMG CoA reductase. Semin Cell Dev Biol 81:121-128
Qi, Xiaofeng; Schmiege, Philip; Coutavas, Elias et al. (2018) Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex. Science 362:
Engelking, Luke J; Cantoria, Mary Jo; Xu, Yanchao et al. (2018) Developmental and extrahepatic physiological functions of SREBP pathway genes in mice. Semin Cell Dev Biol 81:98-109
Hobbs, Helen H (2018) Science, serendipity, and the single degree. J Clin Invest 128:4218-4223
Muse, Evan D; Yu, Shan; Edillor, Chantle R et al. (2018) Cell-specific discrimination of desmosterol and desmosterol mimetics confers selective regulation of LXR and SREBP in macrophages. Proc Natl Acad Sci U S A 115:E4680-E4689
DeBose-Boyd, Russell A; Ye, Jin (2018) SREBPs in Lipid Metabolism, Insulin Signaling, and Beyond. Trends Biochem Sci 43:358-368

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