Mycobacteria are important pathogens in humans and other animals, and include Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). The treatment of TB and other infections caused by mycobacteria is often limited to a few drugs. In 2021 1.6 million people died from TB and the incidence of multidrug resistant Mycobacterium tuberculosis (MDR-TB) rose by 10% between 2018-2019. Therefore, there is a need to find effective new treatments for these diseases.
Cytochromes P450 (CYPs) are a family of haem containing enzymes - many of which have essential roles in metabolism and the production of virulence factors. CYPs have been exploited as drug targets for the treatment of several diseases including fungal infections, sleeping sickness and cancer (aromatase inhibitors). The interaction of CYPs with inhibitors is well understood and so they present attractive potential new drug targets in pathogenic organisms.
Mycobacteria contain many CYPs – there are 20 encoded in the M. tuberculosis genome. Some of these have been identified as being of interest as potential drug targets. For instance, some have been implicated in the utilisation of cholesterol as a carbon source in the host. This may have important implications in the pathogenesis, virulence and persistence of M. tuberculosis, but is not yet fully understood and the physiological role of the majority of the CYPs in mycobacteria remains unknown.
This project will use a combination of bioinformatic, biochemical and molecular biology approaches to investigate the role of CYPs in these organisms. This combination of techniques will allow the CYP enzymes, along with their redox partners (ferredoxin and ferredoxin reductase), to be characterised in relation to their substrates and inhibitors and gene expression profiles. This project will enable us to further enhance our understanding of the CYPs in mycobacteria and to determine their potential as drug targets.
The techniques used will include; protein expression and purification, bioinformatics (comparative genomics), protein structure modelling, molecular biology (cloning, qRT-PCR), recombinant protein production, enzymology (substrate and inhibitor binding), mass spectrometry (analysis of metabolites), structural biology and microbiology (non-pathogenic mycobacteria species).
The studentship will commence in October 2023 and will cover your tuition fees (at UK level) as well as a maintenance grant. In 2022-23 the maintenance grant for full-time students was £17,668 per annum. As well as tuition fees and a maintenance grant, all School of Biosciences students receive access to courses offered by the University’s Doctoral Academy and become members of the University Doctoral Academy
As only one studentship is available and a very high standard of applications is typically received, the successful applicant is likely to have a very good first degree (a First or Upper Second class BSc Honours or equivalent) and/or be distinguished by having relevant research experience.
How to apply:
You can apply online - consideration is automatic on applying for a PhD in Biosciences, with an October 2023 start date.
Please use our online application service at https://www.cardiff.ac.uk/study/postgraduate/research/programmes/programme/biosciences-phd-mphil-md
and specify in the funding section state that you wish to be considered for School of Biosciences funding.
Please specify that you are applying for this particular project and the supervisor.
Information on the application process can be found here
http://www.cardiff.ac.uk/study/postgraduate/applying
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