About the Project
Research interests/description of main research theme:
When muscle is lost in ageing and disease, clinical outcomes are significantly impacted since loss of muscle mass impairs not only locomotory function but also whole-body metabolic health. Indeed the relationship between low muscle mass and increased morbidity and mortality outcomes in ageing and cachectic diseases are extremely robust. Early identification of those at risk of greatest musculoskeletal (MSK) decline is important to ensure optimal interventional strategies can be implemented to prevent and/or delay muscle wasting in these individuals, thereby maintaining MSK health for longer and preventing related co- morbidities. This studentship proposes to identify metabolic signatures of MSK decline in both healthy ageing (sarcopenia) and disease (cachexia), so that at risk individuals can be stratified accordingly. Not only will these signatures allow us to identify those at greatest risk of MSK decline, but disturbances in metabolic phenotypes between healthy and diseased, in addition to between young and old, could potentially uncover underlying mechanisms involved in wasting and hence potential therapeutic or drug targets (for future translational funding) which could be used to normalise this metabolic disturbance and improve skeletal muscle function and hence quality of life.
Throughout the PhD the student will have access to world-class facilities and training. The Clinical, Metabolic and Molecular Physiology research group (UoN) are world leaders in mechanistic and metabolic research studies in MSK disease and healthy ageing. Moreover, the student will have a unique opportunity to learn cutting-edge metabolomics, mass spectrometry and bioinformatics skills from one of the world leading laboratories in this field; Phenome Centre Birmingham. In addition to this, there is the possibility to spend between 3-12 months at Novartis if appropriate to the project goals. This training will provide the student with a wide range of diverse laboratory and analytical skills.
Person Specification
Applicants should have a strong background in physiology and metabolism, and ideally a background or knowledge of the application of mass spectrometry to understanding metabolism. They should have a commitment to research in ageing and musculoskeletal metabolism and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in Biochemistry or Physiology or a a relevant subject.
How to apply
Informal enquiries should be directed to Dr Daniel Wilkinson at [Email Address Removed] or 01332 724850
Applications should be directed to Dr Lisa Fuller (email [Email Address Removed] ). To apply, please send:
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter stating the project you are applying for and highlighting your research experience/capabilities
The University of Nottingham is one of the world’s most respected research-intensive universities, ranked 8th in the UK for research power (REF 2014). Students studying in the School of Life Sciences will have the opportunity to thrive in a vibrant, multidisciplinary environment, with expert supervision from leaders in their field, state-of-the-art facilities and strong links with industry. Students are closely monitored in terms of their personal and professional progression throughout their study period and are assigned academic mentors in addition to their supervisory team. The School provides structured training as a fundamental part of postgraduate personal development and our training programme enables students to develop skills across the four domains of the Vitae Researcher Development Framework (RDF). During their studies, students will also have the opportunity to attend and present at conferences around the world. The School puts strong emphasis on the promotion of postgraduate research with a 2-day annual PhD research symposium attended by all students, plus academic staff and invited speakers.
Funding Notes
• 3-year funded studentship through the MRC-ARUK Centre for Musculoskeletal Ageing Research (CMAR). Students should have home or EU status: and have been 'ordinarily resident' in the UK for 3 years prior to the start of the studentship to be eligible for the full award (tuition fees, research support costs, and a tax-free stipend at the Research Council rate). Applicants who have been 'ordinarily resident' in another EU member state may be eligible for a fees only award. Please see RCUK terms and conditions for further information.
This studentship is full-time and will begin on 1st of October 2018
References
References
1) Dunn, W.B., Broadhurst, D., Begley, P., Zelena, E., Francis-McIntyre, S., Anderson, N., Brown, M., Knowles, J.D., Halsall, A., Haselden, J.N. and Nicholls, A.W., 2011. Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nature protocols, 6(7), pp.1060-1083.
(2) Dunn WB, Broadhurst DI, Atherton HJ, Goodacre R, Griffin JL. Systems level studies of mammalian metabolomes: the roles of mass spectrometry and nuclear magnetic resonance spectroscopy. Chem Soc Rev 2011;40:387–426. doi:10.1039/b906712b.
(3) Brook MS, Wilkinson DJ, Atherton PJ. Nutrient modulation in the management of disease induced muscle wasting - evidence from human studies. Curr Opin Clin Nutr Metab Care. 2017
(4) WilkinsonDJ, FranchiMV, BrookMS, NariciMV, WilliamsJP, MitchellWK, Szewczyk NJ, Greenhaff PL, Atherton PJ, Smith K. A validation of the application of D2O stable isotope tracer techniques for monitoring day-to-day changes in muscle protein sub- fraction synthesis in humans. Am J Physiol Endocrinol Metab. 2014 Mar 1;306(5):E571-9
(5) AthertonPJ, Greenhaff PL, Phillips SM, Bodine SC, Adams CM, Lang CH. Control of skeletal muscle atrophy in response to disuse: clinical/preclinical contentions and fallacies of evidence. Am J Physiol Endocrinol Metab. 2016 Sep 1; 311(3): E594-604.
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