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Polmorphisms in cytosolic drug metabolising enzymes: a combined proteomics and modelling approach to clinical impact


Faculty of Biology, Medicine and Health

Manchester United Kingdom Analytical Chemistry Biochemistry Pharmaceutical Chemistry Pharmacology Pharmacy

About the Project

Cytosolic drug metabolising enzymes such as aldehyde oxidase play a pivotal role in metabolism of drugs. However, research into cytosolic enzymes has been relatively neglected in comparison with membrane bound enzymes such as cytochrome P450 (CYP) and uridine 5’-glucuronosyltransferases (UGTs).

In this project, we will use state-of-the-art proteomic techniques to quantify aldehyde oxidase and other cytosolic enzymes, and, in particular, to assess polymorphisms that can affect drug metabolism. We will then populate models of drug metabolism with quantitative information on both wild-type and variant enzymes and determine the effects of polymorphism on drug metabolism and hence optimum drug dosage. The endpoint of the project is a model that can be used to bring clinical benefit to patients.

Entry Requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in biochemistry, chemistry, pharmacology or another laboratory-based science subject. Confidence in the used of Microsoft Excel is highly desirable.

 For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Pharmacy and Pharmaceutical Sciences.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit www.internationalphd.manchester.ac.uk


Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website).
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”

References

Quantitative proteomics of clinically relevant drug-metabolizing enzymes and drug transporters and their intercorrelations in the human small intestine
N Couto ZM Al-Majdoub, S Gibson, PJ Davies, B Achour, MD Harwood, G Carson, J Barber, A Rostami-Hodjegan, G Warhurst,
Drug Metab. Dispos. 2020, 48: 245-254.
Characterization of CYP2B6 K262R allelic variants by quantitative allele-specific proteomics using a QconCAT standard
J Barber, MR Russell, A Rostami-Hodjegan, B Achour, J Pharm. Biomed. Analysis 2020, 178: 112901.
Proteomic Quantification of Human Blood–Brain Barrier SLC and ABC Transporters in Healthy Individuals and Dementia Patients
ZM Al-Majdoub, H Al Feteisi, B Achour, S Warwood, S Neuhoff, A Rostami-Hodjegan, J Barber, Molecular Pharmaceutics 2019, 16: 1220-1233

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