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. We successfully applied this approach in our study of AMPK signaling (Coccimiglio et al. 2020). We are currently developing models of resistance-exercise-responsive signaling. For the experimental approach, we use electrical stimulation of cultured myotubes under physoxia to mimic exercise, followed by measuring detailed time courses of signaling.

Funding: Natural Sciences and Engineering Research Council of Canada, Canada Foundation for Innovation, BC Knowledge Development Fund, research contracts with biotechnology companies.

Collaborators: Derek Bingham (SFU Statistics and Actuarial Science), David Campbell (Carleton University)

Exercise induces numerous biochemical and biophysical stimuli to skeletal muscle cells. The cell signaling network senses and integrates these stimuli, and coordinates fitness-promoting adaptations.

Video: talk at the Society for Redox Biology and Medicine Annual Conference

November 19, 2020

The AMPK signaling network in skeletal muscle (Coccimiglio & Clarke 2020 PLoS Comp Biol).