Prof T Maxwell
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
Antimicrobial resistance (AMR) is a major threat to mankind. DNA gyrase is a bacterial type II topoisomerase, and a well-validated target for antibacterials, including the highly-successful fluoroquinolone antibiotics (FQs); but resistance to these drugs is a serious problem. We are investigating potential replacements for FQs. Microcin B17 (MccB17) is a ~3-kDa post-translationally modified peptide produced by Escherichia coli strains harbouring the MccB17 plasmid. MccB17 kills other bacteria by targeting gyrase via a mechanism related to that of FQs: it stabilises the covalent gyrase-DNA cleavage complex, which leads to double-stranded chromosomal breaks and cell death. However, its mode of action is different from that of FQs making it an attractive prospect for developing novel gyrase-targeted antibiotics. We would like to explore the development of other compounds targeting the MccB17-binding site, but this is currently not possible without knowledge of the gyrase-MccB17 complex structure.
The aims of this project are to achieve a molecular understanding of the mode of action of microcin B17 on DNA gyrase and to harness this knowledge for the development of new antibacterial agents. We propose a variety of structural and molecular biology approaches to tackle this problem that will give the student a broad experience of research methods. These will include: mutagenesis, cloning, biochemical and biophysical assays, and structural biology methods (X-ray crystallography and Cryo-EM).
This project has been shortlisted for funding by the Norwich Biosciences Doctoral Training Partnership (NRPDTP). Shortlisted applicants will be interviewed as part of the studentship competition. Candidates will be interviewed on either the 8th, 9th or 10th January 2019.
The NRP DTP offers postgraduates the opportunity to undertake a 4-year research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP students undertake a three-month professional internship (PIPS) during their study. The internship offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. Students with, or expecting to attain, at least an upper second-class honours degree, or equivalent, are invited to apply.
For further information and to apply, please visit our website: www.biodtp.norwichresearchpark.ac.uk
Funding Notes
For funding eligibility guidance, please visit our website: http://biodtp.norwichresearchpark.ac.uk/how-to-apply/funding-and-eligibility. Full Studentships cover a stipend (UKRI rate: £14,777pa – 2018/9), research costs and tuition fees at UK/EU rate and are available to UK and EU students who meet the UK residency requirements.
Students from EU countries who do not meet the UK residency requirements may be eligible for a fees-only award. Students in receipt of a fees-only award will be eligible for a maintenance stipend awarded by the NRPDTP Bioscience Doctoral Scholarships. To be eligible students must meet the EU residency requirements.
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