C. difficile S-layer’s role in antimicrobial resistance

About the Project

Are you interested in a PhD on antibiotic-resistant bacteria and want to develop skills in microbiology, structural biology, advanced microscopy, and antibiotics research while unravelling how a bacterial “armour” helps pathogens resist antibiotics and host defences?

Clostridioides difficile is the leading cause of healthcare-acquired diarrhoea worldwide. This highly antibiotic-resistant pathogen exploits antibiotic-induced disruption of the gut microbiota to cause disease. As resistance to first-line and last-resort drugs for treating C. difficile infections is increasing, we urgently need to understand how C. difficile evades antimicrobials to improve current therapies or design new ones.

We recently determined the structure of the protein crystal-like surface layer (S-layer) that surrounds the bacterial cell. We found this “armour” to be more tightly packed than previously assumed, raising the question of how molecules enter and leave the cell through the tight S-layer. Moreover, we have also shown that the S-layer protects against host defences and provides antibiotic resistance, but the mechanisms remain unknown.

In this PhD, you will use molecular biology, genetics, biochemistry, structural biology and microscopy to understand how Clostridioides difficile’s crystalline surface layer (S-layer) contributes to antimicrobial resistance. You will test whether the S-layer acts as a molecular sieve (excluding molecules by size) or a molecular sponge (sequestering antimicrobials), as a mechanical reinforcement of the cell envelope, or a scaffold for proteins that degrade/modify antimicrobials. You will combine structural biology and advanced microscopy to see how antimicrobials interact with the S-layer and, and investigate the role of S-layer in antibiotic-induced lysis.

You will work in a lab environment that includes postdoctoral researchers and other PhD students, with regular collaboration between the supervisors’ groups. You will be supervised by Prof Paula Salgado, an expert in the structure and function of C. difficile’s S-layer and its role in virulence, with support from Prof Henrik Strahl providing expertise on bacterial cell envelope biology and antimicrobial resistance. This project will give you transferable skills in microbiology, structural biology and imaging, and strong career prospects in infectious disease and antimicrobial resistance research.

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).

(You can check that you meet Newcastle University English Language requirements using this link - International Students: English Language Requirements | Newcastle Uni | Newcastle University)

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