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Innate antimicrobial host defence peptides as protective modifiers in atopic dermatitis


   College of Medicine and Veterinary Medicine

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  Prof D Davidson, Dr Richard Weller, Dr D Clarke  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

Background:
Atopic Dermatitis (AD) is a common and distressing skin disease, for which early onset and a chronic relapsing nature necessitate safe, long-term treatments. Topical corticosteroids, the principal treatment, have harmful long-term side-effects and can mask or even worsen skin infections. In addition, individuals for whom these treatments become ineffective, require systemic therapies with potentially severe side-effects. New treatments are needed, designed around greater knowledge of this disease, with skin barrier integrity identified as a key target.
Skin barrier damage in AD is caused by environmental factors, genetics and infections, including proteases produced by the characteristic AD skin-infecting bacteria Staphylococcus aureus. We have discovered that human beta-defensin (hBD)2 protects skin barrier integrity against S. aureus protease damage.
Importantly, AD skin has impaired production of hBD2. Our new discovery therefore suggests that this resultant loss of antibacterial hBD2 barrier is critically compounded in AD by loss of hBD2-mediated protection of a healthy, effective skin barrier.

About the project:
This interdisciplinary British Skin Foundation-funded project will take Cell Biology, Chemistry, and Immunology focused approaches to evaluate mechanisms by which hBD2 can protect skin barrier integrity. With joint supervision from Inflammation Biology, Chemistry, and Clinical departments, the student will mechanistically evaluate the protective effects of hBD2 against harmful bacterial products and on modulating skin barrier function and inflammatory responses. Working with cultured skin models in vitro and ex-vivo, this PhD project will also include use of mass spectrometry, cellular and secretome proteomics, molecular biology, histology, confocal microscopy, and live cell imaging. The project will lay the foundation for future development peptide analogues, optimised around the critical functions of hBD2 identified, with both barrier-enhancing and microbicidal functions, and potential as safe, long-term, complementary or alternative therapeutics for AD.

The student will be principally located in the MRC Centre for Inflammation Research at the University of Edinburgh; a world-class research environment at the interface between biological and medical science, with multidisciplinary groupings focused on inflammation, infection, disease and repair. The Centre is based within the Edinburgh Medical School (ranked in the UK top 5; REF2014) in the outstanding facilities of the Queen’s Medical Research Institute at the site of the Royal Infirmary of Edinburgh hospital, maximising future translational opportunities.

Funding Notes

The successful applicant will be awarded a 3 year studentship, which includes their stipend, tuition fees (at the UK/EU rate), and contributions towards travel and research costs for their PhD project.

The studentship will be awarded competitively. Applicants should hold at least an upper second class degree or equivalent in a relevant discipline (e.g. biology, immunology, biochemistry). Applicants should submit the following documents to [Email Address Removed]: (i) Personal statement about their research interests and their reasons for applying; and (ii) CV.

References

Applicants should also arrange for two academic referees to submit letters of reference via email before the deadline. All documents should be submitted no later than 5 pm on 19th February 2018. Short-listed candidates will be notified by email.

Informal enquiries can be sent via email to Donald.Davidson@ed.ac.uk
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