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Defining the Epigenome in Tendon Ageing


Project Description

This project will identify epigenetic-based molecules for potential as biomarkers and therapies for tendon ageing and tendinopathy in both man and horse by taking a ‘One Health’ approach. We have previously identified epigenetic molecules which effect both tendon ageing and tendinopathy in both man and the horse. This study will add to our knowledge of the epigenetic molecules which change in tendon ageing and may therefore impact the age-related tendon disease. We will undertake ATACSeq on young and old tendon in equine and human samples and use our other epigenetic datasets plus available data sets online and from collaborators to determine the tendon ageing epigenomic landscape for the first time.
You will learn computational bioinformatics techniques to analyse individual datasets and those that enable integration of multiple epigenetic platforms. Thus you will develop skills in multiple omics platforms. Additionally you will learn a range laboratory-based techniques including qRT-PCR, tissue culture, ATACSeq, DNA and RNA extraction, and mechanistic studies using epigenetic modifying chemicals. The latter will involve testing some of your findings using in vitro 3D tendon culture techniques (human and horse) and epigenetically modifying chemical agents. As such this is a multi-disciplinary project dry and wet lab skills, providing an opportunity to develop skills that will be vital for future Biosciences Research.
You will experience a ‘One Health’ approach as applied to tendon ageing through the use equine and human datasets, cells and tissues. This would provide you with an interdisciplinary, collaborative approach to research, preparing you to meet the challenges inherent in the renewed momentum for ‘One Health’
Candidates with either a computational and/or biological background are welcome to apply as full interdisciplinary training will be provided. PhD supervisors have expertise in musculoskeletal epigenetics as well as computational biology; modelling and systems biology.

HOW TO APPLY
Applications should be made by emailing with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – clearly stating your first choice project, and optionally 2nd and 3rd ranked projects, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University. Applications not meeting these criteria will be rejected.
In addition to the CV and covering letter, please email a completed copy of the Additional Details Form (Word document) to . A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.
Informal enquiries may be made to

Funding Notes

This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£15,009 for 2019-20). The PhD will start in October 2020. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. Please note, there are 2 stages to the application process.

References

Donor age affects proteome composition of tenocyte-derived engineered tendon. BMC Biotechnology 18:2 (2018)

Systems approaches in osteoarthritis: Identifying routes to novel diagnostic and therapeutic strategies. J Orthop Res 35(8): 1573-1588 (2017)

Cross platform analysis of transcriptomic data identifies ageing has distinct and opposite effects on tendon in males and females. Sci Rep 13 Oct, 7: 14443 DOI:10.1038/s41598-017-14650-z (2017)

MicroRNA profiling in cartilage ageing Int J Genomics. ID 2713725, 11 (2017)

Serum snoRNAs as biomarkers for joint ageing and post traumatic osteoarthritis, Scientific Reports DOI: 10.1038/srep43558 (2017)

Decoding the regulatory landscape of ageing in musculoskeletal engineered tissues using genome wide DNA methylation and RNASeq Plos One DOI:10.1371/journal.pone.0160517 (2016)

Age-related changes in mesenchymal stem cells identified using a multi-omics approach Eur Cell Mater. Feb 8;31:136-59

Insulin-like growth factor binding protein (IGFBP6) is a cross-species tendon marker. European Cells and Materials (In Press) (2019)
Molecular habituation as a potential mechanism of gradual homeostatic loss with age, Mechanisms of Ageing and Development 169 (2018) 53–62

Systems modelling ageing: From single senescent cells to simple multi-cellular models. Essays in Biochemistry, 61(3), 369-377 (2017)

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