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The Vitamin D receptor and musculoskeletal ageing: a multi-modal approach.

Project Description

Research interests/description of main research theme:

Vitamin D deficiency is highly-prevalent and has been linked - mainly through population epidemiology - to musculoskeletal (MSK) decline in both ageing, and age-related diseases. Nonetheless, mechanistic links between Vitamin D deficiency and MSK health remain poorly defined. Vitamin D exerts many of its cellular actions through the vitamin D receptor (VDR). We have recently found that loss-of-function and gain-of-function of the VDR stimulated skeletal muscle atrophy and hypertrophy, respectively, in rat electroporation models. These data add to, and further, evidence from transgenic models of VDR knockout (KO) illustrating that the VDR regulates skeletal muscle mass. Moreover, in the same study, we showed that VDR expression was reduced in older humans, while expression of the VDR increases in line with muscle mass gains in response to resistance exercise. Collectively, all available data suggest Vitamin D and Vitamin D receptor dependent regulation of muscle mass (our data, autonomously so).

Vitamin D-deficiency and altered VDR regulation has been implicated in MSK ageing and many age-related diseases. This maybe for many reasons e.g. poor diet, reduced sunlight exposure and deranged processing of Vitamin D molecules to bio-active receptor binding steroid forms (in addition to age-related dysregulation of VDR gene expression). However, follow-on research is needed to define links between Vitamin D status, VDR and MSK health. The present project will; 1) identify novel links between Vitamin D status and MSK ageing, using existing ageing/exercise/immobilization/COPD bio-banks; 2) determine Vitamin D, and Vitamin D-independent effects on muscle mass using a pre-existing cell model of VDR knockdown (lentivirus-mediated sustained VDR loss-of-function previously generated and sustained, in the host-lab); 3) determine if Vitamin D deficiency leads to exercise maladaptation(s).

Person Specification

Applicants should have a strong undergraduate background in biological sciences subjects, and ideally, some background in skeletal muscle metabolism and physiology. They should have a commitment to research into musculoskeletal ageing, and hold or realistically expect to obtain, at least an Upper Second Class Honours Degree in a relevant subject. In addition, a relevant Master’s degree would be preferable. Individual’s should be commited to the conduct of clinical studies, but crucially, should also expect to undertake a significant amount of analytical lab work and biostatistics.

How to apply

Informal enquiries should be directed to Prof Philip Atherton ()

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

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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