The functional role of long non-coding RNA CASC20 in modulating bone formation in musculoskeletal disease. at University of Sheffield on FindAPhD.com

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Prof M Wilkinson No more applications being accepted Funded PhD Project (European/UK Students Only)

About the Project

Total hip replacement (THA) is the current definitive treatment for arthritis, with a lifetime incidence of THA of 9 to 16% in northern European population (1). Heterotopic ossification (HO), the development of lamellar bone within the soft tissues around the joint, is a common cause of persistent pain and stiffness after THA (2 3), and affects up to 43% of patients (4 5). Current treatment for established HO comprises excision of the affected tissue, and carries a high risk of recurrence. Available prophylaxis for HO comprises perioperative treatment with either high-dose non-steroidal anti-inflammatory agents or radiotherapy (6). Both approaches have substantial side-effects that reduce their utility and acceptability (7).

The overall aim of this PhD studentship is to explore the function of CASC20 in modulating bone formation using cell signalling and epigenetic analysis. The specific objectives are to determine: 1) Where CASC20 is expressed in human musculoskeletal tissues; 2) Regulatory mechanisms and signals of CASC20 expression; and finally 3) How CASC20 affects target cell function.

Training in sample retrieval and processing will be delivered by Mark Wilkinson and Diane Swift in Sheffield. Training in specific molecular biological techniques will be delivered by Endre Kiss-Toth and David Young and their respective teams in Newcastle. Bioinformatics training will be provided by the Newcastle Bioinformatics Support Unit.

Interviews will be held on the 29th March in Sheffield

Funding Notes

Funded by the MRC/Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA). Students should have home or EU student status and have been 'ordinarily resident' in the UK for 3 years prior to the start of the studentship to be eligible for the full award (tuition fees, research support costs and a tax-free stipend at the Research Council rate). Please see RCUK terms and conditions.

Candidates should have or expect to hold a first or upper second class honours degree in Biological Sciences or an equivalent degree.

To apply, please download application form from the CIMA website (http://www.cimauk.org/training)

References

1. Ackerman IN, Bohensky MA, de Steiger R, et al. Lifetime risk of primary total hip replacement surgery for osteoarthritis from 2003-2013: A multi-national analysis using national registry data. Arthritis Care Res (Hoboken) 2017 doi: 10.1002/acr.23197
2. Brooker AF, Bowerman JW, Robinson RA, et al. Ectopic ossification following total hip arthroplasty. Incidence and method of classification. J Bone Joint Surg 1973;55-A(8):1629-32.
3. Eggli S, Rodriguez J, Ganz R. Heterotopic ossification in total hip arthroplasty: the significance for clinical outcome. Acta Orthop Belgica 2000;66(2):174-80.
4. Neal B, Gray H, MacMahon S, et al. Incidence of heterotopic bone formation after major hip surgery. ANZJ Surg 2002;72(11):808-21.
5. Wilkinson JM, Stockley I, Hamer AJ, et al. Biochemical markers of bone turnover and development of heterotopic ossification after total hip arthoplasty. J Orthop Res 2003;21(3):529-34.
6. Vavken P, Castellani L, Sculco TP. Prophylaxis of heterotopic ossification of the hip: systematic review and meta-analysis. Clin Orthop Relat Res 2009;467(12):3283-9. doi: 10.1007/s11999-009-0924-5
7. McCarthy EF, Sundaram M. Heterotopic ossification: a review. Skeletal Radiol 2005;34(10):609-19.

Where will I study?

University of Sheffield

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The functional role of long non-coding RNA CASC20 in modulating bone formation in musculoskeletal disease.

University of Sheffield Department of Oncology and Metabolism