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Stratification of osteoarthritis to improve equine welfare


Project Description

Horse Trust Equine Clinical Scholarship Grant

Location: Liverpool and Leahurst Veterinary Campus

Studentship start date: summer 2019

Stipend: Starting stipend of £14,140 or enhanced for a veterinary surgeon to £22,000 plus student fees at UK/EU rates

Osteoarthritis is one of the leading welfare issues in horses in the UK, and results in substantial morbidity and mortality. Although diagnosis has improved greatly in recent years with advances in diagnostic imaging, it is still difficult to determine with any accuracy how a case may progress or respond to treatment. In addition, treatment is limited and therapies currently are only symptomatic.

This studentship aims to identify small non-coding RNAs in synovial fluids and serum which will be used to identify horses with early OA, to stratify horses with OA into disease subtypes, and identify targets for OA treatment. Specific small non-coding RNAs which distinguish subtypes of OA will be developed into clinically applicable assays. Longitudinal clinical studies will then be performed to identify the potential for small non-coding RNAs to identify OA at an early stage, and in predicting treatment response. In addition we envisage that some of these small non-coding RNAs will be targets for future OA treatment.

The studentship objectives:
1) Determine the small non-coding RNA profile of OA synovial fluid and serum using an unbiased approach (small RNASeq).
2) Validate a panel of small non-coding RNAs to determine the effects of clinical variables.
3) We will develop an assay that analyses specific, selected biomarkers.
4) Classify the microvesicle population in normal and OA patients and identify small non-coding RNA cross-talk between cells to identify potential treatment targets for early OA.

The student will be trained in a broad context of musculoskeletal biology, molecular biology, in vitro experiments, extracellular vesicle biology and next generation sequencing. Sometime will be spent at Nottingham Vet School and with a micrRNA assay company in Vienna.

Training will include:
• Training on sample collection, sample preparation for small RNA sequencing
• Bioinformatics analysis of sequencing data
• Research specific skills: cartilage, synovium and bone biology and osteoarthritis (OA), bioinformatics and molecular biology techniques in OA
• Statistics
• Generic research skills: critical thinking, IT skills, scientific integrity, ethics, project and time management, scientific writing and public engagement;
• Personal and professional skills: personal effectiveness, communications skills, networking and teamwork, management and leadership, understanding of research context.

The Institute of Ageing and Chronic Disease is fully committed to promoting gender equality in all activities. In recruitment we emphasize the supportive nature of the working environment and the flexible family support that the University provides. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.

Eligibility: Candidates must hold a degree in a discipline relevant to musculoskeletal biology and/or a veterinary qualification. Overseas candidates may apply, but please contact us to discuss the difference in fee rates.

Applications: Interested candidates should send a CV and covering letter by email to Professor Mandy Peffers with a copy to

Funding Notes

Funding: This is a 3 year studentship, generously funded by the Horse Trust. It includes a stipend starting at £14,140/£22,500 and increasing each year. Research expenses and student fees at Home/EU rates are included.

References

1. Ireland, J.L., et al., Factors associated with mortality of geriatric horses in the United Kingdom. Prev Vet Med, 2011. 101(3-4): p. 204-18.
2. Ireland, J.L., et al., Disease prevalence in geriatric horses in the United Kingdom: veterinary clinical assessment of 200 cases. Equine Vet J, 2012. 44(1): p. 101-6.
3. Tonge, D.P., M.J. Pearson, and S.W. Jones, The hallmarks of osteoarthritis and the potential to develop personalised disease-modifying pharmacological therapeutics. Osteoarthritis Cartilage, 2014. 22(5): p. 609-21.
4. Peffers, M.J., X. Liu, and P.D. Clegg, Transcriptomic profiling of cartilage ageing. Genom Data, 2014. 2: p. 27-8.
5. Balaskas, P., et al., MicroRNA Profiling in Cartilage Ageing. Int J Genomics, 2017. 2017: p. 2713725.
6. Peffers, M.J., et al., Transcriptome analysis of ageing in uninjured human Achilles tendon. Arthritis Res Ther, 2015. 17: p. 33.
7. Pease, L.I., et al., Cross platform analysis of transcriptomic data identifies ageing has distinct and opposite effects on tendon in males and females. Sci Rep, 2017. 7(1): p. 14443.
8. Steinbusch, M.M., et al., Serum snoRNAs as biomarkers for joint ageing and post traumatic osteoarthritis. Sci Rep, 2017. 7: p. 43558.
9. Choudhuri, S., Small noncoding RNAs: biogenesis, function, and emerging significance in toxicology. J Biochem Mol Toxicol, 2010. 24(3): p. 195-216.
10. McIlwraith, C.W., et al., Biomarkers for equine joint injury and osteoarthritis. J Orthop Res, 2017.
11. Murata, K., et al., Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis. Arthritis Res Ther, 2010. 12(3): p. R86.
12. Hong, B.K., et al., MicroRNA-143 and -145 modulate the phenotype of synovial fibroblasts in rheumatoid arthritis. Exp Mol Med, 2017. 49(8): p. e363.
13. Li, Y.H., et al., Identification of synovial fluid microRNA signature in knee osteoarthritis: differentiating early- and late-stage knee osteoarthritis. Osteoarthritis Cartilage, 2016. 24(9): p. 1577-86.
14. Miyaki, S. and M.K. Lotz, Extracellular vesicles in cartilage homeostasis and osteoarthritis. Curr Opin Rheumatol, 2018. 30(1): p. 129-135.
15. Kolhe, R., et al., Gender-specific differential expression of exosomal miRNA in synovial fluid of patients with osteoarthritis. Sci Rep, 2017. 7(1): p. 2029.
16. Probert, C., et al., Tracking extracellular vesicle RNA: a tool for the discovery of novel therapeutic targets in cancer metastasis. European Urology, 2017. In review.
17. McIlwraith, C.W., et al., The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the horse. . Osteoarthritis Cartilage, 2010. 18(Supp 3): p. S93-105.

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