PhD Studentship: Understanding and enhancing the physiological resilience of older adults to improve health-span: a focus on skeletal muscle.

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Medicine
Location:  UK Other
Closing Date:  Monday 22 April 2024
Reference:  MED2003

Principal supervisors:  

PhD 1 - Prof Philip Atherton (School of Medicine) – [email protected]  

PhD 2 - Prof Paul Greenhaff (School of Life Sciences) – [email protected]  

PhD 3 - Prof Bethan Phillips (School of Medicine) – [email protected]  

Funded by the Dunhill Medical Trust (https://dunhillmedical.org.uk/ ) as one of their Multiple PhD Studentship Awards, we have three fully-funded (stipend at UKRI rates, PhD fees (for UK nationals only) and research costs) three-year full-time PhD’s available, each to start on the 1st October 2024.  

Each of these projects is based around the common theme of enhancing the physiological resilience of older adults, with a specific focus on skeletal muscle.

Programme description: Loss of resilience describes enhanced vulnerability to, and impaired recovery from stress events when compared to a robust [youthful/healthy] state; and is commonly encountered with advancing age. With ageing populations around the world, and the associated rise in years spent in ill-health, there is an urgent need to understand the mechanisms underpinning this loss of physiological resilience, and potential strategies to mitigate these declines. Although a recent national GIRFT (Getting It Right First Time) report suggests that improving frailty management could save the NHS >£600-million/year, furthering understanding of the biological mechanisms driving reduced resilience to inform on precision mitigation strategies (i.e., for the right people at the right time) could in fact have a much bigger impact. This impact would favour not only on healthcare systems but also older individuals, their support networks and society as a whole. Evidence suggests that skeletal muscle deterioration, including metabolic and functional decline, is a core driver of reduced resilience in older adults both with and without disease. Indeed, skeletal muscle weakness is at the fore of both frailty (the clinical term encompassing loss of resilience) and sarcopenia (age-associated losses of muscle mass and function) definitions. A devastating consequence of reduced resilience is that the time people spend in good health (their health-span) is now much shorter than overall lifespan; an issue that we aim to help address through this collection of PhD’s.

PhD descriptions: 

PhD 1 – Drug repurposing is an emerging avenue of research in the field of Geroscience; a field whose stated aim is to “accelerate research into the basic mechanisms driving ageing which could lead to improved clinical interventions”. Based at the University of Nottingham Medical School at Derby (UNMSD; Royal Derby Hospital Centre), this PhD is focussed on exploring the impact of an already-licensed mechanistic target of rapamycin (mTOR) inhibitor (which has been shown to attenuate sarcopenia in animal models of ageing) on muscle growth and function in both community-dwelling older adults and orthogeriatric patients. Results from this PhD will inform on the potential of mTOR inhibition to enhance the resilience of older adults, not only in relation to skeletal muscle but also other organ systems for which favourable pre-clinical data is emerging (i.e., the immune system). As is the case for all of these PhD’s, the successful candidate will learn a wealth of skills relating to human physiology studies/clinical trials and state-of-the-art wet-lab techniques.

PhD 2 - Robust evidence regarding the biological mechanisms responsible for the health benefits of physical activity, and the detrimental impacts of inactivity is lacking. This PhD will aim to address the long-standing debate surrounding the role of habitual physical activity levels in driving ageing processes in multiple organs, with a particular focus on skeletal muscle. The successful candidate will be integrated into a multidisciplinary team dovetailing magnetic resonance imaging, biotechnology and human physiology expertise, which will permit a comprehensive array of endpoints to be quantified over the course of a 6 month controlled physical activity intervention. A specific focus of this PhD project will be understanding the contribution of metabolic and physiological changes in skeletal muscle with altered physical activity levels. This PhD will provide unique training in metabolic physiology and will be based across 3 sites, the Sir Peter Mansfield Imaging Centre and Queens Medical Centre (QMC) on the University of Nottingham University Park campus and the UNMSD.  

PhD 3 – In addition to rehabilitation, which has long been employed as method to enhance recovery from clinical stress events, there is burgeoning clinical and research interest in prehabilitation, an approach employed to prepare individuals for these events. Based at the University of Nottingham Medical School at Derby (UNMSD; Royal Derby Hospital Centre), this PhD will consider the importance of, and methods for the preservation of muscle mass and function in older patient cohorts. With elective surgery a clear and common example of a stress event encountered by older adults, and recognising that physiological resilience is not just preparedness for stress events but also the ability to recover from them, this PhD will focus on practicable pre- and rehabilitation strategies in older surgical patients. Exploring the interaction between novel contractile strategies and nutritional intake, results from this PhD will provide an evidence-base for strategies to be implemented as an adjuvant to standard care in the peri-operative period of older surgical patients.   

All of these PhD’s will benefit from the expertise and experience of multi-disciplinary supervisory teams comprised of discovery scientists and clinical academics.

Further information:

Applicants should have either:

• a minimum of a 2.1 in a relevant undergraduate degree (e.g., Exercise Science, Physiology, Biology, Biomedical Sciences (non-exhaustive list)), OR
• a minimum of a 2.2 undergraduate degree and a relevant Master’s degree.

The ideal candidate will also have experience of human physiology and or laboratory research and an understanding of ageing physiology.

Informal enquiries may be addressed to the programme lead, Prof Bethan Phillips ([email protected] ) or to the principal supervisor for each PhD.

To apply, candidates should send their CV and a short cover letter (<1000 words) outlining why they are applying to be part of this PhD programme and what they believe they can offer to: [email protected] . The email subject line should be: “DMT PHD APPLICATION”. Candidates may apply for more than one of the PhDs listed, but should make this known in their cover letter. Candidates should also provide the contact details for 2 referees, one of whom should be their most recent academic supervisor (or line manager in relevant employment, if applicable). Please note, offers of study will be subject to 2 satisfactory references being received.

Closing Date for Applications: Monday April 22nd 2024, 10:00am 

Provisional Interview Dates: 28th and 29th May 2024

If you will not be able to attend an interview at the University of Nottingham Medical School at Derby on these dates please make this known when you email your application to Prof Bethan Phillips so alternative arrangements can be considered if possible.

PhD Start Date: 1st October 2024, or as soon as possible thereafter.