Project Summary Physical activity (PA) has been shown to improve the overall health of human beings. The molecular mechanisms responsible for the diverse benefits of PA are not well understood. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is being formed to advance knowledge in this area. We propose to conduct comprehensive analyses of the MoTrPAC human PA intervention samples, contribute these data to public databases, help identify candidate molecular transducers of PA and elucidate new PA response mechanisms, and help develop predictive models of the individual response to PA. The Genomic, Epigenomic, and Transcriptomic assay site at Icahn School of Medicine at Mount Sinai and New York Genome Center (ISMMS GET) provide the infrastructure, assay and analysis expertise and experience to support this large-scale, comprehensive analysis of molecular changes associated with endurance and resistance exercise. ISMMS GET aims are to 1. Work with the MoTrPAC Steering Committee and Biospecimens Committee to finalize analysis plans and protocols for randomized human clinical trial study; 2. Generate high throughput GET data such as high-depth RNA-seq and Whole Genome Sequencing (WGS), supplemented by additional assay types such as ATAC-seq, Iso-Seq, and CITE-seq based on clinical human samples; 3. QC data and transfer to MoTrPAC Bioinformatics Center (BIC) and perform initial analyses to help ensure data quality; 4. Collaborate with BIC and other MoTrPAC sites to analyze animal and human data from GET and other MoTrPAC analysis sites to identify candidate PA transducers and molecular mechanisms; 5. Integrate various omics data and develop predictive models of PA capacity and response to training in humans; 6. Participate in the preparation of manuscripts and presentations and make the results of the study available to the public using peer-reviewed publications in scientific journals; 7. Make data generated in the study available to the scientific community through MoTrPAC DataHub and Gene Expression Omnibus. The success of GET Sites and the MoTrPAC program will transform insight into the molecular networks that transduce PA into health, create an unparalleled comprehensive public PA data resource, and can provide the foundation for profound advances in the prevention and treatment of many major human diseases.

Project Narrative While physical activity prevents or improves many diseases, the chemical changes that occur in the body and lead to better health are not well known. As a part of a consortium of physical activity research programs working together, we will use advanced technologies to comprehensively study the changes in genes and gene products caused by physical activity. This study can potentially lead to advances in preventing and treating many diseases using physical activity.