Metabolism Core

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PROJECT SUMMARY “Metabolomics” largely consists of metabolic profiling, which is the process of identification and quantification of a large number of metabolites of many different biochemical classes, from diverse biological samples, including cells, culture media, tissue and biofluids. However, to understand the metabolic underpinning of diseases such as cancer, biochemical mechanism(s) must be elucidated, in which case it is necessary to introduce appropriate stable isotope tracers. Although this greatly increases the number of analytes to be quantified, it also enables the retrieval of much more biologically relevant information. This Stable Isotope Resolved Metabolomics (SIRM) approach is a unique specialty of the Metabolism Core, led by PIs with over 40 years of combined expertise in SIRM. The goals of the Metabolism Core are to provide services for a wide coverage of the metabolome with isotopomer and isotopologue analysis, and high throughput protein analysis. To achieve this, we make use of four major analytical platforms, namely (1) high resolution nuclear magnetic resonance (NMR), (2) ultra-high resolution Fourier-transform mass spectrometry (UHR-FTMS), with or without chromatography, (3) ultra-trace elemental analyses by inductively-coupled plasma MS (ICPMS), and (4) Reverse Phase Protein Arrays (RPPA). The Metabolism Core personnel will advise on analytical methods and SIRM-based experimental design with development of additional techniques to address specific issues of identification and quantification and biological interpretation relevant to the COBRE Projects. Because experimental design and sample preparation are integral to the data acquisition and interpretation, the Metabolism Core provides expertise in these and informatics relevant to the SIRM approach. These goals will be achieved according to the following Specific Aims. Specific Aim 1. To provide access and expertise across a wide range of NMR, MS and RPPA technologies to investigators. Specific Aim 2. To provide experimental design, sample processing, and support to the investigators for data reduction, metabolic pathway, and biochemical mechanism analyses. Specific Aim 3. To develop and implement new methods to enhance metabolic capabilities relevant to the COBRE Projects. This Core will support the young investigators by providing advanced analytical technologies and expertise in the metabolic requirements for cancer development and behavior.