Profiling and Mapping Core

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Profiling and Mapping Core B Project Leaders: Kyu Rhee and D. Branch Moody Co-investigators: Jacob Mayfield ABSTRACT - Profiling and Mapping Core B Modern infectious disease research relies fundamentally on genomic maps of the major pathogens. With the recent development of whole-organism metabolomics profiling tools, comprehensively mapping the M. tuberculosis (Mtb) metabolome is now feasible. Core B supports mass spectrometry-based profiling of Mtb metabolites to support Projects 1, 2 and 3 that focus on discovery, drugs and diagnostics, respectively. The Core will carry out whole-organism lipidomic and metabolomic profiling, archive datasets and use modern bioinformatic methods to generate metabo-lipidomic maps of Mtb. Maps are comprised of a structured listing of all metabolite subclasses, a list of all named metabolites within each class, and links of all named metabolites to mass values and other biological variables. We previously generated the MycoMap Database, which is the largest existing map of 183 mycobacterial metabolite classes linked to ~195,000 accurate mass values. We will now expand the database by adding newly discovered lipids generated in Projects 1, 2 and 3. Supporting Projects 1 and 2, we will solve the Mycolate Outer Membrane Lipid Map, which describes compounds located at the host-pathogen barrier and involved in drug penetration. Supporting Projects 1 and 3, the core will measure metabolite variation among Mtb strains from South African patients to generate the Human Mtb Strain Lipid Variation Database. This database will describe the prevalence and variation of lipids among strains circulating in human communities to identify lipids under control by host selection and to support diagnostics development.