1. Cell biology of exercise training adaptations
The biological mechanisms by which humans adapt to exercise training remains an unresolved challenge. It is well established that intracellular signaling systems sense the biochemical and biophysical stressors of exercise and change the expression levels of fitness-promoting genes. But how the "dose" of exercise, i.e., its volume and intensity, are encoded by the signaling systems and decoded by transcriptional control systems remains poorly understood. We hypothesize that the exercise dose is encoded in the signaling "dynamics," i.e., their activities over time, which in turn are decoded by transcription factors that determine the gene expression programs. Since it is challenging to directly measure signaling dynamics in exercising humans, we explore this hypothesis by collecting signaling data using an "in vitro model of exercise" and by developing and studying computer models of the intracellular signaling network. To date, we have studied several established exercise-responsive signaling systems, including AMP-activated protein kinase (AMPK), focal adhesion kinase (FAK), hypoxia-inducible factor-1 (HIF-1), and mechanistic target of rapamycin (mTOR). We seek to further develop and validate our in vitro model of exercise, which involves culturing myotubes on a substrate whose stiffness reflects muscle tissue, and then exposing the cells to combinations of electrical stimulation (to induce contraction), hypoxia (to mimic the drop in oxygen levels during exercise), and heating (to mimic increased muscle temperatures). We sample cells over time and measure signaling, which provides quantitative data that inform the parameter values of our computer models. While the focus of this project is the experimental analysis, the student can undertake some computational work too if interested.
Research area, student roles & skills
Research area: I direct the Laboratory for Quantitative Exercise Biology, which seeks to build predictive models for optimizing exercise training for health, fitness, rehabilitation, and physical performance goals. The lab features three lines of inquiry: exercise-responsive cell signaling, quantifying and modeling training loads, and evidence-based exercise programming.
Student roles:
The student will assist with ongoing projects related to studying exercise-responsive signaling dynamics using the in vitro exercise model. The student will assist on all facets, including culturing cells, seeding cells for experiments, administering the in vitro exercise model, collecting and processing samples, and conducting assays to measure signaling (typically immunoblot or ELISA). The student will be trained and supervised by a senior graduate student. As the student progresses in skill and confidence, they will be assigned more complex tasks.
The student will also do some literature reviewing and present updates in lab meetings, and write a final technical report. Depending on interests and abilities in computational work, the student may be tasked with running some modeling analyses.
Skills required:
Essential qualities are a keen interest and curiosity for exercise and muscle biology and cell signaling. The project is therefore suitable for students from diverse backgrounds; however, those who are pursing kinesiology, exercise/sport science, or life science degrees would likely best suited.
Desired knowledge: exercise and muscle physiology, cell biology, biochemistry.
Desired skills: basic biochemistry and cellular laboratory skills, such as solution making, pipetting, cell culture, and/or protein assays, are considered assets. Basic computer programming skills in R, Python, or MATLAB are likewise assets.
Attitude: demonstrate evidence of independence, resourcefulness, and persistence in resolving challenging problems.