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PhD Research Project

Identifying novel regulators of mitochondrial biogenesis in human skeletal muscle


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Institution Location



Related PhDs


Liverpool John Moores University
School of Sport and Exercise Sciences
University of Sheffield
Department of Biomedical Science
Liverpool John Moores University
School of Sport and Exercise Sciences
University of Dundee
Division of Cancer Research, Medical Research Institute

Dr A Philp
Applications accepted all year round
Self-Funded PhD Students Only

Background:

Skeletal muscle in a healthy adult accounts for approximately 40% of total body mass. In addition to its primary tasks of maintaining posture, breathing and locomotion, skeletal muscle also represents an important nutrient store and metabolic regulator. Unlike many organs within the body that reach their capacity for growth and function upon maturity, skeletal muscle maintains high levels of plasticity during adulthood, being highly susceptible to common stressors such as physical activity/inactivity, exercise and diet. Compelling epidemiological data clearly demonstrates that muscle functional capacity is fundamental for health span (1), thus understanding the regulation of skeletal muscle at the cellular level holds tremendous therapeutic potential for health and disease.

Within skeletal muscle, mitochondria are vital energy producing organelles, generating ATP from intracellular substrate stores. Mitochondrial biogenesis is a broad term used to describe an increase in mitochondrial content, function and activity (2). At the cellular level this adaptive response represents an increase in transcriptional activity, increased content (proliferation) and an increase in mitochondrial protein synthesis (2). Whilst it is well established that aerobic exercise is a potent stimulator of skeletal muscle mitochondrial adaptation; the mechanistic basis linking muscle contraction to mitochondrial biogenesis is still poorly understood. This project will seek to translate recent in vitro and rodent based work from our laboratory (3, 4) into human exercise models, to identify novel transcriptional and post-translational regulators of mitochondrial biogenesis in human skeletal muscle.






Funding Notes:

The current, self-funded position will run until the position is filled. Research will be conducted under the supervision of Dr Andy Philp in the School of Sport, Exercise and Rehabilitation Sciences at The University of Birmingham. Any informal enquiries can be directed to Dr Philp (a.philp@bham.ac.uk).

The ideal candidate will have a strong background in exercise physiology, metabolism and/or biochemistry, with a proven track record of human volunteer based exercise studies. Experience in analytical techniques to study muscle biochemistry is preferable, however specific training in this area will be provided.


References:

1. Ruiz JR, et al. (2008) Association between muscular strength and mortality in men: prospective cohort study. BMJ 337:a439.
2. Scarpulla RC (2008) Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 88(2):611-638.
3. Philp A, et al. (2011) The PGC-1alpha-related coactivator promotes mitochondrial and myogenic adaptations in C2C12 myotubes. Am J Physiol Regul Integr Comp Physiol 301(4):R864-872.
4. Philp A, et al. (2011) Sirtuin 1 (SIRT1) deacetylase activity is not required for mitochondrial biogenesis or peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) deacetylation following endurance exercise. J Biol Chem 286(35):30561-30570.


Research Assessment Exercise (RAE) 2008 Results


Unit of Assessment: Sports-Related Studies What is the RAE?
FTE Category A Staff Submitted 4* 3* 2* 1* U/C
32.8 25% 35% 30% 10% 0%


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