PhD Research Project: DiMeN Doctoral Training Partnership: Evaluating skin xenobiotic metabolism us

Xenobiotic compounds can be described as external foreign molecules that interact with our tissues and cells. These foreign molecules need to be removed in order to maintain a healthy status and certain organs of the body, such as the liver and skin, contain enzymes that are able to deactivate xenobiotic compounds by converting them into molecules called metabolites. Some xenobiotic metabolites are relatively harmless and can be secreted in the urine and sweat, whilst others can cause toxicity or hypersensitivity that can lead to tissue damage. The abundance and location of xenobiotic metabolizing enzymes in the skin is largely unknown. However, pharmaceutical companies are interested in the presence and activity of these enzymes in the skin because they are instrumental in the detoxification of drugs.

In this project we aim to measure the expression and activity of xenobiotic metabolising enzymes and the quantity of their metabolites in the biopsies of human skin or tissue-engineered skin grown in the laboratory and if these are able to instigate hypersensitivity reactions. You will be trained to generate and culture tissue-engineered human skin models using cell culture techniques and then examine the expression of several key metabolising enzymes at the gene (qPCR) and protein (Western blot) level using molecular techniques. Immunohistochemistry will be performed to determine where these enzymes are expressed in the different layers of the epithelium and HPLC and mass spectroscopy will be used to quantify the levels of metabolites.

The data generated will also feed directly into an existing collaboration with LJMU on mathematical modelling of xenobiotic metabolism and metabolite production in skin. The experimental data will inform the development of a new mathematical modelling system that ultimately aims to predict the quantities and location of the metabolites produced from any given xenobiotic compound within the skin. You will be given the opportunity to validate the mathematical simulations using the tissue-engineered model. This project offers the student an opportunity to contribute to a multidisciplinary team that involves scientists, mathematicians and clinicians working within the Northern Health Sciences Alliance to improve drug safety.

This studentship offers the opportunity to work on a multi-disciplinary, cross-cutting research project between researchers based at the Integrated Bioscience Group at the University of Sheffield, and those based in The Institute of Translational Medicine at The University of Liverpool. The student will also have the opportunity to collaborate with systems biologists at Liverpool John Moores University who will use the data generated in an iterative process to model disease processes in order to create predictive patters of toxicity.

Supervisors

Dr Craig Murdoch (University of Sheffield)
Dr Parveen Sharma (University of Liverpool)
Dr Steve Webb (Liverpool John Moores University)
Dr Helen Colley (University of Sheffield)

Funding Notes

DiMeN DTP studentships are funded for 3.5 years and include:

- Tax-free maintenance grant set at the UK Research Council's national rate.
- Full payment of tuition fees at the Home/EU rate.
- A Research Training Support Grant to support your research studies.

Successful Home students will receive a full studentship. EU students will be considered for a full studentship/fees only support depending on the excellence of their qualifications and their employment/residency status.

Please carefully read the instructions on eligibility and how to apply at our website and use the link on the page to submit an application: http://www.dimen.org.uk/how-to-apply/application-overview