PROJECT SUMMARY: VDDRC MASS SPECTROMETRY (MS) AND PROTEOMICS CORE The MS/Proteomics Core provides cost-effective, state-of-the-art instrumentation and expertise to investigators in the Vanderbilt Digestive Disease Research Center (VDDRC). This core leverages the expert personnel and cutting edge instrument facilities located in the Vanderbilt Mass Spectrometry Research Center to provide specialized services to VDDRC members. This core will be used for identification and quantification of small molecules, identification, characterization, and quantification of proteins, and biomolecular tissue imaging and profiling. Fifty-eight VDDRC investigators have used the core extensively during the current funding period for digestive disease-related projects leading to 73 peer- reviewed original publications. Services used include: analytical method development, assistance with experimental design, inductively coupled MS, multiplex quantitative proteomics with isotope tagging methods, phosphoproteome characterization, identification of post-translational modifications, elemental analysis by ICP-MS, molecular profiling, tissue imaging, and bioinformatics analysis. Core personnel perform assays for investigators and provided a formalized training program to 45 trainees from VDDRC Member laboratories on the theoretical and practical aspects of MS during the current funding period. The small molecule/metabolite component of the Core is run as an open-access facility in which users can choose to prepare their samples and operate the instruments. Proteomics samples are submitted to the core for analysis by proteomics staff after consultations between the investigator and core staff on the most appropriate experimental design, sample preparation and instrumental analysis methods. Administrative staff monitor the use of the instrument facilities by investigators and prepare reports on utilization for use by the Administrative Core. The core has 25 mass spectrometers available to users, in addition to specialized instrumentation for advanced analyses. The Specific Aims of the Core are to: 1) Provide access to state-of-the-art mass spectrometry equipment for analysis of small molecule drugs and endogenous metabolites (host and microbial), including targeted and discovery metabolomics, in an open-access analytical facility; 2) Provide access to a state-of-the-art proteomics facility for identification, characterization, and quantitation of proteins and whole proteomes in digestive disease-related samples; 3) Provide access to a pioneering imaging mass spectrometry facility for spatial localization of proteins, peptides, lipids, metabolites, and drugs in GI tissues; 4) Provide professional guidance on experimental design, development of analytical assays, and data interpretation; 5) Train users on digestive diseases sample preparation, instrument operation, and data analysis; 6) Train users on bioinformatics analysis of complex proteomic data; 7) Promote interactions ...