CNS-Met Metabolomics Core

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Neurological disorders and central nervous system (CNS) injuries show clear metabolic defects, which in turn disrupts bioenergetics balances, redox status, and neurotransmitter biosynthesis that are required for maintaining, synaptic activity, neuronal homeostasis, and neuroinflammation. For these reasons, CNS metabolism research has generated interest from those studying Alzheimer’s disease, traumatic brain injury, epilepsy, spinal cord injury, Parkinson’s disease, and others. Modern metabolomics allows for the profiles of hundreds of metabolites from a single sample. It is both informative and transformative, supports both hypothesis-generating and hypothesis-driven research. Current applications of metabolomics include, molecular basis of metabolic diseases, biomarker discovery, disease prediction, drug responses, and personalized medicine. The overarching goal of the CNS-Met Metabolomics Core is to make cutting-edge metabolomics and mitochondrial energetics techniques and analyses available to CNS-Met Research Project Leaders (RPL) and pilot project PIs. The available expertise and instrumentation are well-aligned with the RPL proposals. The core directors have worked with each RPL to generate exciting preliminary data. The core will engage with, assist in experimental design, run samples, train personnel, and analyze brain metabolism data. The CNS-Met Metabolomics Core will support the talented RPLs in the area of CNS metabolism and enhance their success in competing for NIH R-level grants. To achieve these goals, the core will Aim 1: Provide experimental design consultation and project-specific study planning. The core has worked closely with the RPLs, and will continue to do so, on experimental design, data processing, and biostatistical analyses. Proper experimental design and sample preparation will lay the foundation for a successful metabolomics experiment. Aim 2: Provide metabolomics expertise and training. The core will house an Agilent 5977B GCMS, 2) Agilent 6545 quadrupole time of flight LC/CE-QTOF, and 3) a Seahorse Biosciences XF24e and XFe96 Flux Analyzers as well as Oroboros O2KFluorometer. The core will run samples, assist, train, and/or supervise data analysis from basic data reduction, incorporating procedural control, normalization, pathway ontology matching, data interpretation, and offer possible next steps. Aim 3: Perform sample processing, technical analyses, and data reduction-interpretation-presentation. The core will assist users by performing sample preparation, instrument operation, mass spectrometry peak matching to metabolites with a known compound library, sample normalization, and statistical analyses. The core will utilize integrated processes established by core leadership from experimental design though rapid and consistent sample acquisition, sample fixation, sample extraction, data reduction, statistical analysis, data analysis, and biological interpretation to ensure the success of the CNS-Met RPLs and pilot project PIs.