Pre-receptor regulation of glucocorticoid target genes in human skin

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 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) and this regulates cell function (e.g. growth, development, signalling) in tissues such as fat, muscle and liver but the effects of 11?-HSD1 in human skin are unknown. Previous research has demonstrated increased 11?-HSD1 levels in skin from older people1 and in sun-exposed compared to sun-protected human skin2. However, the ability of 11?-HSD1 to regulate GC target genes in human skin has not been investigated.

<p>This project aims to investigate 11&beta;-HSD1-mediated regulation of GC target genes in human skin.</p> <p>You will treat human skin samples with vehicle, cortisone (11&beta;-HSD1 substrate), cortisol (11&beta;-HSD1 product) or cortisone and an 11&beta;-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 11&beta;-HSD1 and 11&beta;-HSD1-regulated gene expression will also be evaluated in temporal artery biopsies from patients with giant cell arteritis.</p> <h3>References</h3> <ul> <li>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.</li> <li>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.</li> </ul>

<p>Please note these are not standalone projects and applicants must apply to the PhD academy directly.</p> <p>Applications can be made at any time. You should complete an <a href="https://medicinehealth.leeds.ac.uk/faculty-graduate-school/doc/apply-2">online application form</a> and attach the following documentation to support your application.&nbsp;</p> <ul> <li>a full academic CV</li> <li>degree certificate and transcripts of marks (or marks so far if still studying)</li> <li>Evidence that you meet the programme&rsquo;s minimum English language requirements (if applicable, see requirement below)</li> <li>Evidence of funding to support your studies</li> </ul> <p>To help us identify that you are applying for this project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Cardiovascular and Metabolic Disease as your programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> </ul>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The minimum requirements for this programme in IELTS and TOEFL tests are: &bull; British Council IELTS - score of 7.0 overall, with no element less than 6.5 &bull; TOEFL iBT - overall score of 100 with the listening and reading element no less than 22, writing element no less than 23 and the speaking element no less than 24.

<p>For further information please contact the Faculty Graduate School<br /> e:<a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p>