PROJECT SUMMARY/ABSTRACT The overall goal of the Systems Biology and Multi-Omics Core (SBMOC, Core C) is to establish local infrastructure in the Indiana Center for Musculoskeletal Health (ICMH) to support the unique and undiscovered technical solutions for advancing genomic and metabolomic applications specifically, in the field of musculoskeletal science. This unique innovation would parallel the adaptation of high-throughput omics approaches well established in oth-er fields such as cancer biology and neurological diseases. This core will address the unique aspects of working with skeletal muscle (e.g., multi-nucleation, predominantly sarcomeric protein), bone (e.g., isolation of osteocytes, osteoblasts, osteoclasts from densely mineralized matrices that are difficult to overcome), and tendon/ligament (e.g., isolation of tendon cells from a tough, fibrous environment). The SBMOC will also serve as an educational hub for ICMH investigators to design musculoskeletal genomics and metabolomics studies, emphasizing training in study design, data integration, interpretation, and insights. The ultimate aim of the core is to use the investigatorgenerated large datasets along with the publicly available data to yield new mechanistic hypotheses and discoveries in the musculoskeletal field by leveraging the computational, bioinformatics, genomic, and metabolomics infrastructure in the Indiana University School of Medicine. SBMOC will be founded as an extension of existing and highly successful institutional cores and centers, namely the Center for Medical Genomics, and the Center for Computational Biology and Bioinformatics, along with a newly established state-of-the-art metabolomics facility. The creation of the SBMOC will allow the three units to coordinate the critical services to all ICMH investigators, including study design, assay selection, data generation, data processing, data interpretation, data integration and data dissemination. In addition to providing critical coordination between these three resources and offering subsidized service rates, the SBMOC will also facilitate new technology and methodology development and implementation which will be crucial to promoting musculoskeletal research. In summary, SBMOC will facilitate musculoskeletal research through the following aims: (1) Provide and further develop state-of-the-art genomics services to meet the needs of ICMH members to advance their musculoskeletal research programs; (2) Perform and customize state-of-the-art metabolomics services to meet the needs of ICMH investigators; (3) Integrate datasets from various omics platforms to address research hypotheses and develop novel research directions; and (4) Facilitate development of ICMH investigator knowledge of, and training in, omics-based approaches to enable expansion of systems-level experiments. The SBMOC will provide the musculoskeletal research community with cutting-edge genomic and molecular biology services, bioinformatics/bi...