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Mitochondrial quality control in skeletal muscle ageing and response to exercise


Project Description

Research interests/description of main research theme:
Applications are invited for a 3-year PhD studentship, fully funded by the MRC-ARUK Centre for Musculoskeletal Ageing Research (CMAR), to work in the group of Dr. Lai at the University of Birmingham on a collaborative project with Prof. Atherton at the University of Nottingham and Prof. Sakamoto at the Nestle Institute of Health Sciences.

Skeletal muscle mitochondrial density and function is critical to maintain musculoskeletal health (e.g. strength/mass/aerobic capacity) across the lifespan. However, muscle mitochondrial function declines with age (and inactivity) and conversely, is improved by exercise through enhanced turnover i.e. mitochondrial biogenesis, and removal of damaged mitochondria via mitophagy. The mechanisms regulating the turnover of mitochondria during ageing, and in response to exercise, remains unclear. AMPK, a “master regulator” of cell metabolism, has been implicated skeletal muscle ageing and adaptations to exercise, including adaptive mitochondrial biogenesis. The physiological link between AMPK and mitophagy arises from data on muscle-specific AMPK knock-out mice that have impaired induction of autophagy and who accumulate enlarged mitochondria in aged muscle (1). Furthermore, recent studies reported that AMPK-ULK1 pathway may be responsible for exercise-induced mitophagy, suggesting that altered activity of AMPK (e.g. with ageing and exercise) is central to mitochondrial quality control. All in all, Poor mitochondrial quality control is likely to be a critical factor contributing to senescence and muscle dysfunction in ageing. Here we proposed to investigate mitochondrial quality control activity by comparing young and old rodent muscles. Since exercise is known as the best regime for ‘anti-ageing’, we aim to study the molecular mechanisms of how exercise-activated signalling pathway, such as AMPK, can promote mitophagy. This information is critical for future development of health promoting strategies/nutrients/drugs.

The project will utilise novel mitophagy reporter (MitoQC) mice (2) to: [1] investigate the effect of ageing and exercise on muscle mitophagy in vivo and [2] to determine the role of AMPK in mitophagy during ageing and in response to exercise. The student will be trained to use advanced molecular and biochemical approaches, including CRISPR/Cas9 and proteomics, to solve the research questions. You will also take the advantage of the in-housed Mitochondrial Profiling Centre (led by Dr. Lai) to investigate mitochondrial function and enjoy the highly collaborative research activities between the Lai lab and the Clinical, Metabolic and Molecular Physiology research group, led by Prof. Atherton at the University of Nottingham.

This project includes an industrial placement at the Nestle Institute (Lausanne, Switzerland). The collaborative activities between CMAR and our industrial partner at Nestle Institute will afford you to experience diverse and world-leading research environments. Supervisors on each site will ensure the student obtaining the most updated knowledge and skill-sets to perform his/her research.

Person Specification
Applicants should have a strong background in molecular biology and metabolism with a hands-on experience working in wet labs , and ideally a background in biochemistry and with experience of handling rodents . They should be very enthusiastic and motivated, have a commitment to pursue the highest quality of research in the field of ageing and exercise muscle biology and hold or realistically expect to obtain at least an Upper Second Class Honours Degree or a first grade Master degree in a relevant subject of Biochemistry or Physiology.

How to apply
Informal enquiries should be directed to Yu-Chiang Lai through

Applications should be directed to Lisa Fuller (email – ). To apply, please send:
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.

This studentship is full-time and will begin on 1st of October 2019
Interviews will take place on 22nd March 2019.

Funding Notes

To be eligible for a full award, a student must have no restrictions on how long they can stay in the UK and have been ordinarily resident in the UK for at least 3 years prior to the start of the studentship. Students from EU countries other than the UK are generally eligible for a fees-only award. To be eligible for a fees-only award, a student must be ordinarily resident in a member state of the EU; in the same way as UK students must be ordinarily resident in the UK. Further information on eligibility is available online - View Website

References

(1) Bujak AL et al., (2015) AMPK activation of muscle autophagy prevents fasting-induced hypoglycemia and myopathy during aging. Cell Metab. 21(6):883-890

(2) McWilliams TG et al., (2018) Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand. Cell Metab. 27(2):439-449

How good is research at University of Birmingham in Sport and Exercise Sciences, Leisure and Tourism?

FTE Category A staff submitted: 34.40

Research output data provided by the Research Excellence Framework (REF)

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