Exercise-responsive cell signaling
Exercise training adaptations manifest at the cellular level, in particular in skeletal muscle tissue. In response to aerobic endurance training, for example, muscle cells build mitochondria and express contractile protein isoforms that are more efficient. In response to resistance training, muscle cells add protein and volume (hypertrophy) and are able to contract more forcefully.
A longstanding question in exercise physiology is how the whole-body stressor of exercise is distilled into basic biochemical and biophysical stressors that operate at the cellular level, and how the cells sense, integrate, and ultimately adapt to these stressors. In addition, how do cells sense and adapt to the duration and intensity of execise (i.e., its "dose")? Applications of improved understanding could include exercise professionals being able to design workouts that optimally target specific physiological adaptations.
We hypothesize that the duration and intensity of exercise are encoded in the dynamics of the biochemical signaling network that operates within skeletal muscle cells. To explore this hypothesis, we employ computational modeling and in vitro experimental approaches. The computational models represent the biochemical mechanisms of signaling, which we use to study how different input patterns are converted to output dynamics. Experimentally, we use electrical stimulation of cultured myotubes under physoxia to mimic exercise, followed by measuring detailed time courses of signaling.
To date, we successfully applied this approach in our study of AMPK signaling (Coccimiglio et al. 2020), and we have developed a kinetic model of leucine-mediated signaling and protein metabolism (manuscript in preparation). We are developing a mechanotransduction model for inferring signaling across muscle fibres in an exercising muscle.
