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To determine the effect of surgical induced systemic inflammation on immobilisation induced declines in muscle protein synthesis and immune cell function


Project Description

Immobilisation and inflammation are independently associated with significant muscle atrophy and when simultaneously present, result in catastrophic muscle mass loss that is associated with increased mortality. Muscle mass is maintained by the balance between muscle protein synthesis (MPS) and breakdown (MPB), with immobilisation rapidly supressing MPS resulting in muscle atrophy. Similarly, inflammation directly influences pathways modulating MPS, with ICU patients demonstrating reductions in MPS and muscle loss 100-fold increase in VL Il-6). Systemic inflammation is therefore likely to have significant damaging effects on whole body muscle, in addition to bed rest immobilisation post-surgery. Besides muscle, systemic inflammation often results in immune suppression. This immunoparesis is poorly understood, however there is an appearance of abnormal neutrophils with impaired function whose frequency is associated with increased susceptibility to infection and sepsis. As such there are no effective, feasible interventions to limit muscle atrophy after surgery or trauma, with the burden of systemic inflammation on muscle dysregulation and immunosuppression unknown.

This project will use novel stable isotope techniques developed to enable simultaneous measurement of MPS and neutrophil turnover during post-surgical recovery. Throughout the PhD the applicant will have access to worldclass facilities and receive training from leading experts within the field of musculoskeletal research. Being based across two schools at the UoN the student will receive training on advanced metabolic and molecular biology techniques and learn cutting-edge mass-spectrometry techniques at the forefront of the field. Requiring blood and muscle biopsies to be collected the student will be familiarised with clinical skills and further spend valuable time at the Birmingham BRC developing skills and knowledge in inflammatory research and immunosuppression

Person Specification

Applicants should have a strong background in physiology, metabolism, and ideally a background in molecular biology. They should have a commitment to research in analytical sciences and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a subject of scientific background.

How to apply

Informal enquiries should be directed to

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 21st 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] Wilkinson DJ, Franchi M V, Brook MS, Narici M V, Williams JP, Mitchell WK, et al. A validation of the application of D2O stable isotope tracer techniques for monitoring day-to-day changes in muscle protein subfraction synthesis in humans. Am J Physiol Endocrinol Metab 2014;306:E571- 9. doi:10.1152/ajpendo.00650.2013.

[2] Brook MS, Wilkinson DJ, Mitchell WK, Lund JN, Szewczyk NJ, Greenhaff PL, et al. Skeletal muscle hypertrophy adaptations predominate in the early stages of resistance exercise training, matching deuterium oxide-derived measures of muscle protein synthesis and mechanistic target of rapamycin complex 1 signaling. FASEB J 2015;29:4485–96. doi:10.1096/fj.15-273755.

[3] Varadhan KK, Constantin-Teodosiu D, Constantin D, Greenhaff PL, Lobo DN. Inflammationmediated muscle metabolic dysregulation local and remote to the site of major abdominal surgery. Clin Nutr 2017:4–11.

How good is research at University of Nottingham in Biological Sciences?

FTE Category A staff submitted: 90.86

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

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