PROJECT SUMMARY: Mass Spectrometry Core (formerly Metabolomics Core) Diabetes and its related endocrine and metabolic disorders are characterized by disruption of homeostasis. Aberrant signaling cascades involving protein post translational modifications such as phosphorylation, accumulation of potentially toxic lipid species, and altered flux of intracellular metabolites are among the abnormalities that constitute the diabetic milieu. The DRC Mass Spectrometry Core, an expanded version of the former Metabolomics Core, provides rigorous mass spectrometry-based proteomics and metabolomics analyses to DRC investigators that include quantification, structural characterization, and functional characterization of diabetes-related biomolecules. The Core increases efficiency and cost effectiveness by providing centralized, standardized mass spectrometry analyses to study molecular mechanisms of the pathogenesis of diabetes, its risk factors, and its complications. A major goal of the core is to promote use of mass spectrometry (MS) methods in diabetes research through training, collaboration, development, service, and dissemination. Specific objectives of the Core are: 1) to provide and maintain functional MS systems for diabetes-related studies; 2) to consult with DRC investigators regarding how MS can advance their research programs; 3) to perform service-related MS analyses for diabetes investigators, such as quantifying target analytes, obtaining spectra for structural identification, and assisting with mass spectra interpretation; 4) to develop new MS methods; and 5) to provide training to students and fellows in principles and use of MS systems. During this past funding period, this Core, operating as the Metabolomics Core, provided services to 34 different DRC member laboratories, including 3 P&F recipients, and the >11,000 hours of Core service supported the publication of 90 papers. Through a substantial institutional investment, the capabilities of this Core have increased prompting a name change to DRC Mass Spectrometry Core. The services offered by the Mass Spectrometry Core reflect the evolving bioanalytical needs of DRC investigators, including 1) quantitative study of protein expression, including targeted assays from clinical samples; 2) quantitative assessment of protein-protein interactions; 3) characterization of post translational modifications; 4) elucidation of the biological functions of proteins or protein groups; 5) targeted metabolomic services; 6) broad surveys of multiple metabolic pathways and quantification of pathway metabolites via untargeted metabolomics; and 7) high-throughput, quality-controlled measurements of analytes in large sample sets from clinical studies. The Mass Spectrometry Core thus leverages substantial institutional investments in instrumentation and analytical expertise to promote new discoveries and scientific progress in diabetes research at the Washington University DRC.