11β-hydroxysteroid dehydrogenase type 1: a novel target to improve wound healing in diabetes

Project description

 Background

 Glucocorticoid (GC) steroid hormones (commonly used to treat a range of inflammatory disorders) cause many adverse effects in skin including thinning, collagen loss, impaired 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 skin are poorly understood. Type 2 diabetes is an unmet clinical need of global importance. National incidence in the UK is approaching 10% and costs the NHS £9 billion annually with chronic wounds and infections resulting in >7000 amputations a year. Previous research has demonstrated increased 11β-HSD1 activity during normal wound healing1 and improved wound healing in healthy aged mice lacking 11β-HSD12 but the role of 11β-HSD1 in wound healing impaired by diabetes has not been investigated.

Aim

This master by research project aims to investigate 11β-HSD1-mediated regulation of wound healing in a mouse model of diabetes. Methods: You will use quantitative PCR following mRNA extraction and cDNA synthesis to analyse gene expression during wound healing in healthy mice compared to a genetic mouse model of diabetes (leptin-receptor deficient). Immunohistochemistry will also be used to visualise changes in wound healing, inflammation and collagen remodelling.

References 

1. Tiganescu, A. et al. Increased glucocorticoid activation during mouse skin wound healing. J Endocrinol. 2014, 221(1), pp.51-61.
2. 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 to the grad school. 

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.