Understanding an unexpected mechanism of development of antimicrobial resistance in bacteria (AMR)

About the Project

Antimicrobial resistance (AMR) of pathogenic bacteria threatens to become critical and requires immediate action to understand the mechanisms leading to it. Often AMR is achieved through resistance mutations in the protein targeted by a particular antibiotic. However, the supervisory team recently discovered (2020. PLoS Pathogens 16, e1008672 https://doi.org/10.1371/journal.ppat.1008672) that development of MRSA (methicillin-resistant Staphylococcus aureus) strictly requires mutations in RNA polymerase (RNAP). Methicillin inhibits cell wall synthesis, while RNAP is the enzyme that performs the first step of gene expression – transcription, which is not a target for methicillin. The mechanisms of how different single amino acid substitutions in RNAP lead to the MRSA phenotype remains a mystery.

We hypothesise that mutations in RNAP are required as an adaptation strategy for survival under the antibiotic stress. These mutations may reprogramme gene expression and/or alter the crosstalk of RNAP with other cellular machineries, such as translation, DNA replication, maintenance of chromosomes organisation and their segregation. The project aims to explain this phenomenon, and thus shed light on MRSA development and on similar adaptation mechanisms of other drug-resistant pathogenic bacteria.

We will apply a multidisciplinary approach, which includes (but is not limited to) cutting-edge biochemistry of purified RNAPs and factors, their structural analysis using CryoEM, bacterial genetics, fluorescent and atomic-force microscopies, high throughput RNA-sequencing techniques and accompanying statistical analysis.

Prof Nikolay Zenkin (Primary Supervisor; https://www.ncl.ac.uk/cbcb/staff/profile/nikolayzenkin.html), Dr Winterhalter (Secondary Supervisor; https://www.ncl.ac.uk/medical-sciences/people/profile/charleswinterhalter.html) and Prof Simon Foster (Third Supervisor; https://sheffield.ac.uk/biosciences/people/academic-staff/simon-foster) are the leaders in characterisation of molecular mechanisms of gene expression and in bacterial physiology and genetics. The project will be based in the Centre for Bacterial Cell Biology of Newcastle University, which brings together leading scientists in the field of biology of bacterial cell. The Centre is situated in the new building fitted with the state of the art equipment, and provides unique scientific environment.

Funding

Students who have, or are expecting to attain, at least an upper second-class honours degree (or equivalent) in a relevant subject, are invited to apply. Funding is available for Home (UK) students to cover tuition fees, a tax-free stipend at the UKRI rate (indicative amount in year 1 in 2026-27, £21,805) and research costs, for four years. Applicants normally required to cover International fees will have to cover the difference between the Home and the International tuition fee rates. There is no additional funding available to cover NHS Immigration Health Surcharge (IHS) costs, visa costs, flights etc.

Funding for this studentship is awarded on a competitive basis and is not guaranteed; availability will depend on the outcome of the selection process and subject to final approval by the University.

HOW TO APPLY

Please complete the following application form – Google Form

Applicants can only apply for 1 project; any additional applications will not be accepted.

Applicants should send the following documents to FMSstudentships@newcastle.ac.uk:

• a CV (including contact details of at least two academic (or other relevant) referees).
• a Cover letter – stating your project choice, as well as including additional information you feel is pertinent to your application.
• copies of your relevant undergraduate degree transcripts and certificates.
• a copy of your IELTS or TOEFL English language certificate (where required)
• a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE

Please submit your documents in the following format only:

• each document should be submitted as a separate attachment and should be named as follows: candidate surname, candidate name – document type. For example: Jones, Jamie – CV; Jones, Jamie – cover letter.
• Please submit .pdf documents where possible for your CV, cover letter, transcripts and certificates. Do not submit photos of certificates.
• Do not combine documents into one pdf. You may zip separate documents into a zip file to send via email if required.
• When emailing your application, please use the email subject header: FMS PhD Application 2026

Applications not meeting these criteria may be rejected.

Informal enquiries may be made to the lead supervisor of the project you are interested in.

The deadline for all applications is 12 noon BST (UK time) on Wednesday 20th May 2026.