Pre-receptor regulation of glucocorticoid target genes in human skin

Project description

Background

Glucocorticoid (GC) steroid hormones (commonly used to treat inflammatory disorders eg giant cell arteritis - a condition affecting older people) cause many adverse effects in skin including thinning, collagen loss, poor wound healing and increased infection risk. GC are activated by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and this regulates cell function (e.g. growth, development, signalling) in tissues such as fat, muscle and liver but the effects of 11β-HSD1 in human skin are unknown. Previous research has demonstrated increased 11β-HSD1 levels in skin from older people1 and in sun-exposed compared to sun-protected human skin2. However, the ability of 11β-HSD1 to regulate GC target genes in human skin has not been investigated.

Aim

This master by research project aims to investigate 11β-HSD1-mediated regulation of GC target genes in human skin.

Methods

You will treat human skin samples with vehicle, cortisone (11β-HSD1 substrate), cortisol (11β-HSD1 product) or cortisone and an 11β-HSD1 inhibitor. GC target gene expression will be measured by quantitative PCR following mRNA extraction and cDNA synthesis. Corresponding changes in protein expression will be confirmed by immunohistochemistry. Using these methods, correlations between 11β-HSD1 and 11β-HSD1-regulated gene expression will also be evaluated in temporal artery biopsies from patients with giant cell arteritis.

References

Tiganescu, A. et al. Localization, age- and site-dependent expression, and regulation of 11beta-hydroxysteroid dehydrogenase type 1 in skin. J Invest Dermatol. 2011, 131(1), pp.30-6.

Tiganescu, A. et al. 11beta-Hydroxysteroid dehydrogenase blockade prevents age-induced skin structure and function defects. J Clin Invest. 2013, 123(7), pp.3051-60.

Entry requirements

This project is available immediately to both Home/EU rate applicants and International applicants who are able to self-fund their studies.

You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject. This project would suit a student with a strong background molecular and cellular biology.

Candidates whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study, the Faculty minimum requirements are

• British Council IELTS - score of 6.5 overall, with no element less than 6.0
• TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

How to apply

To apply for this position potential applicants should initially contact the lead supervisor, Dr Ana Tiganescu directly.

Following this, please submit a formal application by completing a Faculty Application form and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School.

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly by email. 

If you have already applied for other positions, or any scholarships, using the Faculty Scholarship Application form you do not need to complete this form again. Instead, you should email to inform us you would like to be considered for this scholarship project.