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White Rose BBSRC DTP studentship: Probing a novel allosteric binding site in Mycobacterium DNA gyrase to tackle TB and antimicrobial resistance


   Faculty of Biological Sciences

  , Dr Martin McPhillie,  Friday, January 07, 2022  Competition Funded PhD Project (Students Worldwide)

Leeds United Kingdom Biochemistry Computational Chemistry Genetics Synthetic Chemistry

About the Project

Human pathogenic bacteria, e.g. Mycobacterium tuberculosis (TB), show increasing resistance to current antibiotics. Antimicrobial resistance (AMR) is probably the biggest current threat to human health; it is estimated that 10 million people per year could die because of AMR by 2050. AMR is compounded by the lack of new antibacterial agents coming onto the market, caused by loss of profitability. Amongst the most successful current antibiotics are fluoroquinolones (FQs), which are widely used in antibacterial chemotherapy, including TB. However, FQs are subject to increasing AMR and alternatives must be found. FQs target DNA gyrase and/or DNA topoisomerase IV, enzymes that are essential in bacteria but absent from humans. We are working with compounds that also target gyrase/topo IV but act in a different way such that cross resistance is avoided. Currently they are unsuitable for humans due to toxicity. Using computational methods, synthetic chemistry, biochemistry/biophysics, microbiological/toxicology evaluation, and structural work, we will develop new, drug-like compounds that retain antibacterial efficacy but that have other properties required for drug leads, including low toxicity. We are specifically targeting TB, which causes extensive mortality/morbidity worldwide. We aim to identify a new series of antibiotic leads with promise for subsequent development as TB drugs.

Funding Note

This studentship is part of the BBSRC White Rose Doctoral Training Partnership in Mechanistic Biology. (https://www.whiterose-mechanisticbiology-dtp.ac.uk/). Appointed candidates will be fully-funded for 4 years. The funding includes:

Tax-free annual UKRI stipend (£15,609 for 2021/22 starts. Awards increase every year, typically with inflation).

UK tuition fees (Around £4,500 per year)

Research Training and Support Grant (RTSG)

Conference and Professional Internships for PhD Students (PIPS) allowances

We aim to support the most outstanding applicants from inside and outside the UK. We are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

Not all projects will be funded; the DTP will appoint a limited number of candidates via a competitive process.

How to apply

Applicants should complete an online application form and attach the following documentation to support their application. 

  • a full academic CV
  • degree certificate and transcripts of marks
  • Evidence that you meet the University's minimum English language requirements (if applicable).

To help us identify that you are applying for this studentship project please ensure you provide the following information on your application form;

  • Select PhD in Biological Sciences as your programme of study
  • Give the full project title and name the supervisors listed in this advert
  • For source of funding please state you are applying for a White Rose BBSRC DTP funded studentship

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