The University of Manchester; PhD Studentship Mechanistic

Dr Costas Demonacos & Dr James Yates

The objective of this project is to understand mechanisms of regulation of drug metabolism processes and allow predictions to be drawn in regards to individualised drug treatment. The studentship provides full support for tuition fees, associated research costs and an annual tax-free stipend at Research Council rates (anticipated to be £13,490). The project is due to commence October 2010 and is open to UK/EU nationals only due to the nature of the funding.

Rationale:  It is essential to understand the rate and extent to which drug metabolising enzymes are affected by steroid treatment in order to determine whether there are any alterations in gene expression during chronic therapy of various diseases such as arthritis, lupus erythematosus, bronchial asthma etc. This project will use biological experimental approaches to generate data that will feed a mathematical model linking the different species involved.

Inter-individual variations in drug response and drug-drug interactions are partly due to variations in the expression of genes regulating drug transport and metabolism, which affect both the pharmacological activity and toxicity of drugs. Understanding the molecular mechanisms involved in the modulation of the expression of enzymes involved in these processes is advantageous for the pharmaceutical industry and clinic since those compounds that affect the expression of metabolising enzymes usually are problematic in the clinic and produce altered pharmacokinetic profiles and drug-drug interactions.

The experimental characterisation and mathematical modelling will provide information regarding the molecular links between nuclear receptors and drug metabolising enzymes, and will increase the safety and personalisation of drug usage.

The project involves a combination of molecular, biological and biochemical methodologies as well as mathematical modelling so would suit an applicant with a strong interest in pharmacokinetics and molecular pharmacology. The study will be conducted within the School of Pharmacy & Pharmaceutical Sciences and involve a placement within AstraZeneca. The successful candidate would develop skills in molecular pharmacology, biochemistry, proteomics and mathematical modeling techniques.

Upon completion, a research career within academia or industry would be anticipated.

Applicants should hold, or expect to obtain, a minimum upper-second honours degree (or equivalent) in the biological sciences, pharmacy, biology, biochemistry or chemistry. Previous laboratory experience in molecular biology or biochemistry would be beneficial.

Please direct applications in the following format to james.k.power@manchester.ac.uk

• A CV, including full details of all University course grades to date.
• Contact details for two academic or professional referees.
• A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and your research experience to date.

Any enquiries relating to the project and/or suitability should be directed to Dr Costas Demonacos at constantinos.demonacos@manchester.ac.uk.  Applications are invited up to and including Thursday 18 February 2010.

http://www.pharmacy.manchester.ac.uk/