Moonshot

MULTISCALE ATHLETE

Bringing scientific understanding to human performance at every scale

credit I-Hsun Wu, UC San Diego

We know that different training regimes and external factors such as sleep and nutrition are important and impact performance, but we don’t know how they work. Through this endeavor, we will investigate the mechanisms of peak performance at scales from the whole body to organs and muscles to the sub-cellular factors that influence how we move, engage, and thrive.
-Andrew McCulloch, PhD, lead investigator

An Interconnected Synergistic Approach:
Athletic performance is the physical and mental whole-body expression of the integrated function of all major physiological systems, including the musculoskeletal, neuroendocrine, and cardiovascular systems. The biological responses of these physiological systems to training, sleep, diet, stress, injury, and other factors depends on the integration of the molecular, multicellular, and extracellular matrix dynamics that determine the functional states of tissues.

credit: I-Hsun Wu, UC San Diego

Project 1, Multiscale Modeling: Multiscale models of musculoskeletal tissue states is adding three-dimensional structure and multicellular and cell-matrix interactions to the cell systems models. These multiscale models will be used to predict how intrinsic biological differences and extrinsic changes affect the physical performance of tissues. The physical tissue stresses associated with training, performance, or injury also modify and regulate tissue states. Hence the multiscale models of tissue state will characterize both how tissue structure and state affect physical performance and how physical performance feeds back to modulate tissue state and structure. This project is lead by Dr. Andrew McCulloch, PhD.

Project 2, Systems Biology, led by Drs. Padmini Rangamani, PhD and Pradipta Ghosh, MD, is creating systems biology models to synthesize molecular and cellular dynamics of the cell signaling and metabolic networks that regulate tissue states. These predictive models, once validated, can be used to predict new experiments and to screen for candidate therapeutic strategies in silico.

Project 3, Mechanobiology, led by Drs. Adam Engler, PhD, and Stephanie Fraley, PhD, is analyzing the mechanoregulatory mechanisms, by subjecting mouse tissues and human tissues to external mechanical forces and physical conditions. To understand the biological determinants of elite performance and accelerated healing, we are making use of unique mouse models that have these traits and engineering tissues derived from athletes.

Project 4, Biomechanics: To formulate and validate mechanistic multiscale models, we will require new experimental measurements of the structural, physical, and biological properties of tissues. Project 4 is creating microstructural constitutive models of tissue biomechanics, we ware measuring the three-dimensional structure and mechanical properties of musculoskeletal tissues. This project is led by Drs. Daniela Valdez-Jasso, PhD, and Andrew McCulloch, PhD.

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