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The molecular basis of human tendon pathologies: Studying both epigenetic and global gene expression profiles

  • Full or part time
  • Application Deadline
    Friday, May 31, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Soft tissue disorders represent the third most common musculoskeletal condition in the UK (18 cases per 1000). These primarily affect tendons: accounting for 30% of all musculoskeletal consultations with a general practitioner and an annual cost of £250M to the NHS. Current therapeutic strategies for tendinopathies are at best ineffective and at worst harmful. The most prevalent, shoulder/rotator cuff tendinopathy (RCT) can lead to long term frailty, pain and reduced levels of physical activity, with the subsequent risk of weight gain. The intrinsic pathogenetic mechanisms underlying the development of tendinopathies are largely unknown however inflammatory mechanisms have recently been implicated functionally in several model systems.

Molecular evidence suggests that many of the key inflammatory/matrix interactions occur in the early stages (acute/subacute) of repetitive tendon micro trauma when patients can be totally asymptomatic. Most autoimmune and inflammatory diseases are associated with epigenetic changes in immune and tissue/stromal cells. Epigenetic molecular adaptations to DNA and histone function can lead to pathology via altered gene regulation, or effect RNA stability. A number of studies have shown that certain genes are abnormally regulated in RCT. However, the regulatory mechanisms and epigenetic factors that underpin these changes are unknown. Studying the epigenetic basis to RCT will enhance our understanding of how this pathology progresses and might pave the way for preventative or therapeutic interventions.

With this in mind, the PhD student would isolate RNA and DNA from human early and late stage RCT samples collected after surgery and investigate global gene expression changes using microarray technology. The student would confirm microarray data using selected qPCR analysis and establish whether DNA methylation changes are responsible for the up or downregulation of genes of interest. Further analyses including chromatin immunoprecipitation followed by ChIP-seq to map common histone modifications (histone H3,H4; H3K9me3,H3K27me3, H4K16Ac, H4K20Me3 ) associated with fibrosis along with RNA sequencing (RNA-seq) to measure whole genome RNA expression may be utilised pending the results of initial microarray analysis.

Benefits

• The Centre has a vibrant post graduate student community and has accreditation from the Royal Society of Biology (RSB) for the training it gives to its science PhD students.
• You will benefit from access to a world-class, Olympic-grade fitness and sports science facilities and life sciences laboratory environment with industry standard research and teaching facilities. You will become a part of a multi-professional team of renowned academics, researchers and clinicians.
• The new Science and Health Building is home to the first education-based Super laboratory (Lab+) for biomedical, pharmacological and analytical sciences.

Training and Development

The successful candidate will receive comprehensive research training including technical, personal and professional skills.
All researchers at Coventry University (from PhD to Professor) are part of the Doctoral College and Centre for Research Capability and Development, which provides support with high-quality training and career development activities.

Entry criteria for applicants to PhD

• A minimum of a 2:1 first degree in a relevant discipline/subject area with a minimum 60% mark in the project element or equivalent with a minimum 60% overall module average.
PLUS
the potential to engage in innovative research and to complete the PhD within a 3.5 years
• a minimum of English language proficiency (IELTS overall minimum score of 7.0 with a minimum of 6.5 in each component)

For further details see: https://www.coventry.ac.uk/research/research-students/making-an-application/

• knowledge and/or experience in the subject
• Candidates should have some knowledge or experience of gene expression and epigenetics
• Candidates should have some knowledge of statistics and data analysis. In order to contextualise the research.
• Candidates may be asked to travel and spend short periods of time at the University of Glasgow where some experiments will take place.

How to apply

To find out more about the project please contact Dr Stuart Raleigh, Director of Studies or Professor Helen Maddock Executive Centre, Centre for Sport, Exercise and Life Sciences (CSELS)

To apply online please visit: https://pgrplus.coventry.ac.uk/

All applications require full supporting documentation, a covering letter, plus a 2000-word supporting statement showing how the applicant’s expertise and interests are relevant to the project.

Interview dates: Will be confirmed to shortlisted candidates

Duration of study: Full-Time – between three and three and a half years fixed term

Start date: September 2019

Funding Notes

Fully funded to UK/EU fee equivalence plus stipend
(please note that eligibility is restricted to UK/EU graduates only)

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