The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is designed to discover and characterize the range of molecular transducers (the `molecular map') that underlie the effects of physical activity (PA) in humans. We formed an interdisciplinary team with the requisite experiences to contribute significantly to the overall success of MoTrPAC. Our Exercise and Physical Activity Collaborative Team (ExPACT) – an alliance of the University of Alabama at Birmingham Center for Exercise Medicine (UAB), Translational Research Institute for Metabolism and Diabetes in Orlando, Florida (TRI-MD), and Ball State University Human Performance Laboratory (BSU) – has extensive experience performing highly-controlled aerobic (AT) and resistance (RT) exercise training clinical trials in healthy and diseased populations. We have a lengthy history of maximizing human biospecimens (muscle, adipose, blood) to reveal molecular underpinnings linked to physiological and clinical outcomes of acute and chronic exercise stimuli. Moreover, the overarching goal of ExPACT is to contribute substantively to successful MoTrPAC planning, execution, and innovation. Phase I (Planning Year) Aim 1. We will effectively collaborate with MoTrPAC leaders and NIH leadership to help guide and finalize the structure and standard operating procedures (SOPs). Aim 2. Leveraging institutional resources committed to ExPACT and our previous experience, we propose to collect pilot biospecimens to facilitate the MoTrPAC Chemical Analysis Sites' ability to optimize analyses. Phase II (Recruitment and Testing Years 2-5) Aim 1. We will enroll 420 sedentary but healthy men and women 18+ y into a rigorously controlled, 12-wk, randomized trial of AT (n=185), RT (n=185), or no-exercise control (CON, n=50). ExPACT geography will enrich MoTrPAC racial, ethnic, urban, suburban, and rural diversity. The design incorporates comprehensive phenotyping to assess fitness and clinical outcomes, and human tissue phenotyping to link the molecular transducers with key biological responses to exercise. Aim 2. Pre- and post- training, we will obtain strategically timed biospecimens before and after acute exercise. To better understand the biological extremes, we will conduct the same acute response studies in highly-trained athletes (AT (n=20) or RT (n=20)). Serial biospecimen collection in CON will allow estimation of biological, seasonal, circadian and methodological variability. Aim 3. To enhance the overall scientific impact of MoTrPAC, we will seek additional funding to conduct innovative ancillary studies, which will markedly augment subject and tissue phenotyping and interpretation of the molecular maps. Phase III (Close-out Year 6) Aim 1. We will complete all ExPACT data entry, quality control, and central deposit procedures in collaboration with the MoTrPAC Coordinating Center, and we will actively contribute to the completion of biospecimen analyses, manuscript writing, and dissemination of results...