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Proteases as mediators of tissue repair

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  • Full or part time
    Dr M Sherratt
    Dr G Lopez-Castejon
    Dr Christopher Platt
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Tissue proteases may be expressed constitutively or in response to injury or disease. In skin, excessive protease activity, either due to ultraviolet radiation (UVR) exposure or intrinsic inflammation is commonly considered to be a key driver of ageing. As a consequence, topical anti-ageing formulations often contain protease inhibitors. However the most effective skin anti-ageing treatments all promote, at least some, protease activity. We, and others, have previously shown that prior exposure of key extracellular matrix assemblies to UVR, enhances their susceptibility to digestion by matrix metalloproteinases (MMPs). Using human skin and skin cell cultures, this PhD project seeks to characterise the role of extracellular proteases in mediating skin repair by testing the hypotheses that: i) extracellular proteases preferentially degrade damaged proteins and , assemblies and ii) targeted protease activity is an important precursor to effective tissue repair. The student will become well versed in inflammation, protease and skin biology, the application of proteomic and transcriptomic technologies and the ethical and practical aspects of recruiting human volunteers in a clinical setting. The studentship is sponsored by Walgreens Boots Alliance and hence there will be ample opportunities for the student to be exposed to the commercial realities of product development and marketing within a large, multi-national commercial environment.

Entry Requirements:
Applicants are expected to hold, or about to obtain, a minimum upper second class undergraduate degree (or equivalent) in cell biology, physiology or biochemistry. A Master’s degree in a relevant subject and/or experience in skin biology/ageing is desirable.

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor.On the application form select PhD Cell Matrix Research.

Funding Notes

Fully funded Studentship through Walgreens Boots Alliance. Studentship funding is for a duration of four years to commence in September 2019 and covers UK/EU tuition fees and an annual minimum stipend (£15,466 per annum 2019/20). Due to funding restrictions the studentship is open to UK and EU nationals only.

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

Hibbert SA, Watson RE, Griffiths CE, Gibbs NK, Sherratt MJ . (2019) Selective proteolysis by matrix metalloproteinases of photo-oxidised dermal extracellular matrix proteins.

Eckersley A, Mellody KT, Pilkington S, Griffiths CEM, Watson REB, O’Cualain R, Baldock C, Knight D, Sherratt MJ. 2018. Structural and compositional diversity of fibrillin microfibrils in human tissues. J. Biol. Chem. 89:109-117.

Palazon-Riquelme P, Lopez-Castejon G. The inflammasomes, Immune guardians at defence barriers. Immunology. 2018 Nov;155(3):320-330

Naylor EC, Watson RE, Sherratt MJ (2011). Molecular aspects of skin ageing. Maturitas. 69:249-256.



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