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Combine advanced imaging and molecular biology to identify microRNA biomarkers of equine osteoarthritis

   College of Medicine and Veterinary Medicine

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  Dr S Taylor, Dr M Clinton  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

Background: There are no reliable methods of diagnosing osteoarthritis (OA) in either humans or horses before radiological evidence of the disease develops, which hinders the effectiveness of therapies and potential preventative measures. A biomarker has been defined as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention. Classical biomarkers such as matrix fragments require the disease process to have begun resulting in irreversible cartilage damage at the time of diagnosis. MicroRNAs (miRNAs) are a type of short non-coding RNA that regulate the expression of various genes. MiRNAs are stable in serum and synovial fluid and have been used in human medicine as biomarkers of various cancers, rheumatoid arthritis and osteoarthritis.

The aim and focus of this project is to establish the suitability of miRNAs to be used as biomarkers of osteoarthritis (OA) of the equine distal interphalangeal joint. Objective one: Determine the basal levels of selected miRNAs (including miRNA 140-5p) in equine sera and synovial fluid collected from horses with distal interphalangeal osteoarthritis identified by low field MRI (figure 1), high field MRI and contrast enhanced CT with histological evidence (figure 2) of cartilage damage (n=10) compared to a control population (n=10). Objective two: Determine the effects of miRNA 140-5p agomir (double stranded miRNA mimic or agonist) on cell culture of equine chondrocytes harvested from normal and diseased distal interphalangeal joints in terms of COL2A1, MMP-13 and ADAMTS-5 gene expression. Evaluate the miRNA response of these normal and diseased chondrocytes when allogenic conditioned serum is applied in cell culture. Objective three: Experimentally validate miRNA:target interactions identified from rna-seq and miRNA target prediction programmes from objective 1 using cells from objective 2.

The prevalence of OA is greater than 50% in horses older than 15 years and up to 80% to 90% in horses over 30 and as such is an important cause of pain, disability and economic loss within the equine industry. MicroRNA identification of horses that are at risk of rapid progression of disease would allow selection of horses that would most benefit from rehabilitation. Another avenue that would directly benefit equine welfare would be the ability of biomarkers to monitor response to therapy.

All PhD students have an assigned principal supervisor, second scientific supervisor(s), pastoral academic supervisor and a member of the PG committee; these comprising the members of the Thesis Committee’ (TC) responsible for monitoring scholar progress. Formal assessment procedures entail: (i) Week 10 - By this stage, the scholar will be expected to have made some progress on understanding research techniques, developing appropriate laboratory skills, and have begun reading the literature. They should produce a brief plan of their first year’s work, in consultation with their supervisors. This research plan should be agreed by both the scholar and the TC and submitted to the School PG Office no later than the 15th week following commencement of the programme; (ii) End of Year 1 - preparation of a first year report comprising a 25 page document (literature review, clear statement of the aims of the project, any significant data obtained during the year) which is assessed by the TC in a viva format. An oral presentation is also made to the committee; (iii) Year 2 - a poster presentation is made and formally assessed at a School-wide poster session. Submission of a thesis plan and timetable for completion to the School PG Office; (iv) Year 3 - a seminar is presented by the scholar as part of the School seminar programme. Presentation of a poster at the annual School Research Student Day. In addition to their formal monitoring role as part of the TC, the supervisor will also be in a position to oversee the programme on a regular basis. The scholar will have regular contact with the supervisors, who will have primary responsibility for organising training in techniques. In addition, the scholar and home supervisors will meet monthly, while meetings with collaborators will take place at least twice yearly. Additional meetings (e.g. by ‘skype’/teleconference/’meeting point’) will be arranged if necessary. Biannual reporting to the funder; The Horse trust will also be required.

The successful applicant will join the RICE Developmental Biology group led by Dr Michael Clinton at The Roslin institute, and Dr Sarah Taylor at the Dick Vet Equine Hospital, University of Edinburgh.

Contact Sarah Taylor ([Email Address Removed]; +44-131-650-6253/6252)

Qualified veterinarians will receive a tax-free stipend of £21,000 annually for 3 years. Student fees will be paid by the sponsor.

Funding Notes

The student must hold a relevant veterinary degree (which permits work as a veterinary surgeon in the UK), or an appropriate science degree from a UK or EU university. In exception circumstances candidates from non-EU countries will be considered. The candidate should wish to pursue a research career in the equine field to improve welfare of equids.

Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to [Email Address Removed]

Please state clearly the title of the studentship and the supervisors in your covering letter.
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