PROJECT SUMMARY/ABSTRACT Nutrition- and obesity-related research is of critical importance given the tremendous impact of metabolic conditions on human health. While nutrition and obesity related research enables investigators to generate many disease-related hypotheses, the technology needed to create disease-relevant models and to test these hypotheses lies outside the expertise of many individual research groups. The Metabolic Phenotyping Core serves as a single, central access point for NORC-H investigators to enable in silico metabolic analyses, model creation in metabolically relevant cell types, and detailed phenotypic characterization of human and model- derived samples. The fundamental activities of the core are divided into three central activities, both supported by expert faculty with extensive experience in all Core activities: 1) in silico metabolic analysis permitted by computational intersection of rich genomics, metabolomics, and proteomics datasets highly relevant to nutrition and obesity; 2) model generation, which brings genomic targeting and modern genome editing to the hands of all NORC-H investigators, and 3) metabolic phenotyping, ranging from metabolomics to whole-animal physiology. Metabolic computational analyses are capable of providing new insights or generating new hypotheses through expertise in the Core with large datasets of genomics, proteomics, and metabolomics in humans and facility with their intersection. Model generation uses state-of-the-art gene targeting resources available at MGH and the Broad Institute, permitting NORC-H members to model disease-related processes in metabolically-relevant primary cells, immortalized cells, and patient-derived inducible pluripotent stem cells. The Core’s battery of customizable, metabolic phenotyping assays can be employed to characterize human tissue and blood samples provided by the investigator or samples generated by the Core’s model-generation activities. The Core has expert capabilities for metabolic computational analyses, metabolomics (mass spectrometry of endogenous metabolites), characterization of metabolism and respiratory activity of cells in culture, analysis of insulin signaling and gene expression, and physiologic characterization of mouse models of human disease. Under the Core, complex analyses and techniques that require expertise and infrastructure that are difficult or impossible for individual laboratories to attain are made readily available to NORC-H investigators. The innovation of the Core, is its ability to provide state-of-the-art analyses to the broad NORC-H membership through a single access point, permitting investigators to ask an innumerable number of nutrition and obesity related research questions with efficiency and economy. The significance of the Core’s activities lie in its ability to encourage both detailed characterization of human samples and to enable translational, mechanistic studies that cannot be conducted in humans. Finally...