PhD BBSRC/CASE Studentship in Veterinary Medicine and Science

Principal supervisor:

Dr Stuart Paine

Other supervisors:

Dr Tracey Coffey and Dr Clive Pearce (LGC Ltd)

Background:

The School of Veterinary Medicine and Science at the University of Nottingham is the first brand new, purpose-built veterinary school in the UK for over 50 years and it is our intent to make significant leading contributions to both veterinary research and teaching within the context of valid relevance and application to the wider veterinary profession.

Research is central to the activities of the School, both in terms of maintaining ourselves at the forefront of national and international efforts in veterinary medicine but also as an integral part of the training and education for undergraduate and postgraduate students.  In the 2008 Research Assessment Exercise, the School of Veterinary Medicine and Science joint submission with the School of Biosciences was ranked first in the country for the power of its research with 95% of its activities classified at an international standard. 

Project:

The use of hepatic metabolic in vitro tools for the prediction of human pharmacokinetics has become a stalwart in the discovery of new drugs over the last decade. These tools are slowly coming on-line for companion animals such as cat and dog but very little has been done with regards to the horse. A suite of in vitro metabolising tools available for the horse would improve equine disease, health and welfare through a mechanistic understanding of how foreign chemicals are metabolised.

UDP Glucuronosyltransferases (UGTs) are the enzymes responsible for the process of glucuronidation, a major part of phase II drug metabolism. Glucuronidation is also the major pathway for the biotransformation of dietary substances, toxins and endogenous substances. The objectives of this project are to obtain the major horse UGT recombinant enzymes and characterize these enzymes using molecular biology techniques. The enzymes will then be phenotyped with suitable drug substrates, and inhibition potential will be measured for commonly used equine drugs against identified substrates of glucuronidation. The in vitro data obtained will be modelled using physiologically-based pharmacokinetics to predict the impact on drug levels and then compared to the clinically observed results.

Techniques used will include Bioinformatics, PCR and cloning, protein expression, purification and verification by dot blot and western blot and testing of commercial human antibodies for immunoreactivity to equine UGT proteins. Phenotyping of model substrates and enzyme kinetics will use mass spectroscopy analysis and Kinetic modelling software. The external partners (LGC LTD) are very interested in understanding the interaction of drug molecules with the horse UGT enzymes as this will allow greater understanding for doping control within the horse racing industry.

Further information

Minimum 2.1 undergraduate degree or 2.2 degree and masters in biological or chemistry subjects.

Informal enquiries: Stuart.Paine@nottingham.ac.uk.

Start Date: October 2013 or ASAP thereafter.

Funding

Studentship available for 4 years from October 2013 and provides a CASE postgraduate stipend, potential funding restrictions apply for non-EU students.

Students should apply online, via the 'Apply’ button below, and include a CV. Queries: postgrad-vet@nottingham.ac.uk. Please quote ref. MED/1183.

This studentship will remain open until filled.