Dr. David Thomson, Department of Physiology & Developmental Biology

Evaluation of academic objectives and project findings

The purpose of this mentoring environment grant was to determine whether the presence of the protein PAS-kinase (PASK) affects muscle growth and/or endurance performance. Our primary model system was the PASK knockout mouse (PASK-KO) and findings from this mouse were compared with wild-type (WT) mice. The project is now completed. The primary research objectives and findings are listed below:

• The PASK-KO mouse colony was established and maintained for nearly 2 years.
• Muscle hypertrophy is not affected in PASK mice.
• Activation of the pro-hypertrophy ribosomal protein S6 was first determined to be elevated in PASK-KO mice after high-frequency muscle contractions, despite the lack of difference in hypertrophy. However, subsequent experiments failed to reproduce the original data.
• Female PASK-KO mice run more in voluntary running cages (contrary to hypothesis) than their wild-type littermates.
• Increased endurance in the PASK-KO females isn’t associated with increased skeletal muscle mitochondria, muscle or liver glycogen content or muscle capillarity.Female PASK-KO mice run more in voluntary running cages (contrary to hypothesis) than their wild-type littermates.
• Forced treadmill running endurance (as opposed to voluntary wheel running activity, above) is not different between PASK-KO and WT mice.
• In-vitro muscle fatigue is not different between PASK-KO and WT mice.

 

Unfortunately, the only reproducible finding in our research was that the female (but not male) PASK-KO mice had increased voluntary running activity. We were unable to discover any skeletal-muscle specific mechanism for the increased running. We suspect that it is likely due to neurogenic factors instead of enhancement of skeletal muscle function per se. Since our research focus area is skeletal muscle, we are no longer actively pursuing further research regarding PASK. Therefore, this project has been completed with the finding that PASK does not play an essential or inhibitory role in muscle endurance or growth.

Participating students and academic deliverables

The students who participated in the work associated with this grant were: Shawn Platt, Zac Olesky, David Sharrah, Jouber Santos, Daniel Atwood. Each of them gained proficiency in several laboratory skills. Shawn presented findings from this work at the Integrative Physiology of Exercise Conference in Miami in September 2010, along with two other students who presented posters on separate projects. He did a fantastic job. My colleagues from other universities were quite surprised that he was only an undergraduate student, as he was very prepared and knowledgeable about the field. Although publication of data from this project in a journal is unlikely (as we could not determine a mechanism for our finding of increased running), Zac and Daniel will both be authors on our next manuscript associated with a separate project which will be submitted for publication this year.

Evaluation of mentoring environment

I currently have 14 undergraduate students working in the laboratory with me. I have found that direct interaction and training from me is crucial in helping them become independent and trustworthy in the laboratory. I dedicate 3 full mornings per week to laboratory research work with the students, oftentimes one-on-one. I have 3 graduate students who are very knowledgeable and help greatly in guiding the undergraduate students. We have weekly lab meetings together, and I also meet regularly with the individual students to go over their data and discuss their progress. While this particular project did not bear the fruit we were hoping for, we have three other lines of research that are very promising, each of which was reported on by undergraduate students at the recent Integrative Biology of Exercise Conference in Denver (October 2012). Overall our work continues to progress very nicely.