Hiding in plain sight: How a multi-drug resistant pathogen evades detection and killing by human neutrophils

About the Project

The Antimicrobial Resistance (AMR) crisis is a leading global health challenge we face in society. AMR is responsible for over a million global deaths per year, a number predicted to increase to ~10 million by 2050. Escherichia coli ranks second on the World Health Organization’s bacterial priority pathogen list due to widespread AMR amongst clinical isolates, being responsible for ~14% of the total deaths attributed to AMR globally. This frightening situation highlights the urgent need to combat AMR and develop novel treatment strategies against E. coli.

Uropathogenic E. coli(UPEC) is the leading cause of urinary tract and bloodstream infections worldwide, responsible for ~80% and ~25% cases of each syndrome respectively - a concern given the risk of affected patients developing life-threatening sepsis. Sepsis is a major global health issue associated with ~50 million cases/year and 20% mortality. UPEC disease progression involves dissemination from the host-gut to the bladder, ascension to the kidneys and, ultimately, bloodstream invasion. UPEC colonises, replicates and persists at these diverse sites through a combination of cellular adhesion, flexible metabolism and evasion of host immunity.

In preliminary work, we discovered that UPEC clinical isolates display a striking ability to block neutrophil migration towards infected organs during bloodstream infection – effectively hiding from the host’s first-line of defence. Neutrophils provide protection against pathogens through engulfment, reactive oxygen species and antimicrobial peptides. UPEC is also capable of evading killing and surviving within neutrophils. However, the mechanisms that underpin this multifaceted immune evasion process are unknown.

This project will dissect the molecular interactions between UPEC and human neutrophils. The student will first isolate human neutrophils and use cell culture to establish a model system of studying the dynamics of UPEC survival within neutrophils. Next, a dual transcriptomic-metabolomic approach will profile the molecular pathways triggered by both UPEC and neutrophils during interaction. Key bacterial genes identified will be “knocked-out” using genetics and tested for a precise role in neutrophil evasion. Lastly, they will explore whether adoptive transfer of “activated” neutrophils that have been exposed to UPEC could restore host defence and promote clearance of immune-evasive UPEC using an in vivo model. This highly interdisciplinary collaborative project at the interface of microbiology, cell biology and immunology offers exceptional training for the candidate to experience a wide range of cutting-edge techniques across the supervisory teams’ labs.

Interested applicants are encouraged to contact the primary supervisor Dr James Connolly (https://www.ncl.ac.uk/medical-sciences/people/profile/jamesconnolly2.html) prior to application.

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 20^th May 2026.