Novel phage-based therapeutics against drug-resistant bacteria. MRC GW4 BioMed DTP PhD studentship for 2026/27 Entry, Department of Ecology and Conservation (Penryn) Ref: 5625

Supervisors

Lead Supervisor:  Professor Edze Westra - University of Exeter - Faculty of Environment, Science and Economy

Co-Supervisors:

Dr Ben Temperton - University of Exeter - Faculty of Health and Life Sciences

Professor Mark Szczelkun - University of Bristol

The GW4 BioMed2 MRC DTP is offering up to 17 funded studentships across a range of biomedical disciplines, with a start date of October 2026.

These four-year studentships provide funding for fees and stipend at the rate set by the UK Research Councils, as well as other research training and support costs, and are available to UK and International students.

About the GW4 BioMed2 Doctoral Training Partnership

The partnership brings together the Universities of Bath, Bristol, Cardiff (lead) and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities, with opportunities to participate in interdisciplinary and 'team science'. The DTP already has over 90 studentships over 6 cohorts in its first phase, along with 80 students over 4 cohorts in its second phase.

The 122 projects available for application, are aligned to the following themes;

• Infection, Immunity, Antimicrobial Resistance and Repair

• Neuroscience and Mental Health

• Population Health Sciences

Applications open on 1 September 2025 and close at 5.00pm on 20th October 2025.

Please note that we may close the application process before the stated deadline if an unprecedented number of applications are received– check our website for details.

Studentships will be 4 years full time. Part time study may also be available.

Project Information

Research Theme:

Summary:

Antibiotic-resistant Pseudomonas aeruginosa is a major global health threat, causing infections that are increasingly difficult to treat. This project will develop next-generation bacteriophage (phage) therapies that target and kill these bacteria, overcoming conventional antibiotic resistance. You will explore how phages can be engineered to maximise effectiveness, understand how bacteria evolve resistance to phages, and use synthetic biology to design precision tools that restore phage sensitivity. This interdisciplinary research integrates microbiology, genomics, and bioengineering to tackle one of the most urgent challenges in infectious disease, offering training in cutting-edge approaches with clear real-world impact. 

Description:

Antimicrobial resistance (AMR) is an urgent global health threat, driving a critical need for innovative therapeutics to control multidrug-resistant bacterial pathogens. Pseudomonas aeruginosa is a major cause of hospital-acquired infections and is inherently resistant to many antibiotics. As conventional treatments fail, bacteriophages (phages) are gaining renewed attention as precision antimicrobials. However, a significant barrier to effective phage therapy is the remarkable ability of bacteria to deploy defence systems, such as CRISPR–Cas, restriction– modification, and abortive infection, to neutralise phages before they can clear infection.

There is an increasing interest in the use of engineered phage genomes to overcome these defences. Yet scaling up production of modified phages remains challenging. Traditional in vivo production in bacterial hosts imposes limitations, including toxicity of certain genetic modifications (e.g., broad-range methyltransferases), the need to use pathogenic strains or species as production platforms, and the release of endotoxins by the production host. To address these obstacles, cell-free synthetic biology systems have emerged as a powerful alternative. These platforms enable assembly, replication and rebooting of non-cognate xenophages entirely in vitro, allowing precise genome editing and epigenetic modification in a controlled environment without the constraints of bacterial viability.

This project will pioneer an E. coli-based cell-free system to generate modified P. aeruginosa phages with enhanced therapeutic properties, building on advanced phage production workflows and cell-free systems developed by Dr. Temperton. The approach will combine genome engineering (e.g., adding anti-defence genes or payloads like toxins or CRISPR-silencing) with epigenomic tailoring (e.g., methylation patterns that evade host restriction). Ultimately, this work aims to produce a robust pipeline for designing and manufacturing bespoke phages that bypass bacterial defences and selectively kill target pathogens.

Research Question:

Can we create a scalable, programmable cell-free platform for producing engineered P. aeruginosa phages with tailored genomic and epigenomic modifications to overcome bacterial defences and improve therapeutic efficacy?

Specific Objectives:

Objective 1: Establish an E. coli cell-free phage production system Addition of non-cognate sigma factors to cell free systems can reprogram E. coli RNA polymerase to recognise xenophage promoters in order to initiate rebooting. Here, the student will adapt and optimise existing E. coli cell-free lysates to reboot P. aeruginosa phages via supplementation with plasmids encoding both sigma factors native to Ps. aeruginosa and novel sigma factors designed through generative AI (e.g. evo2).

Objective 2: Engineer phage genomes to encode counter-defence systems and antimicrobial payloads

Using synthetic biology and in vitro recombination techniques, the student will generate phage genomes incorporating genes that neutralise bacterial defences (e.g., anti-CRISPR proteins) or deliver toxins to enhance bacterial clearance.

Objective 3: Tailor phage epigenomes to bypass restriction-modification defences

The project will explore methods to methylate phage DNA with promiscuous methyltransferases in vitro, building on prior attempts to do this in vivo. This will involve characterising methylation patterns, testing how they impact the efficacy of rebooting, and whether phage modification improves treatment efficacy against resistant P. aeruginosa strains.

Objective 4: Validate engineered phages against clinically relevant P. aeruginosa strains

The student will evaluate the infectivity, replication kinetics, and bactericidal activity of modified phages in vitro against an international panel of clinical isolates of P. aeruginosa, comparing their performance to unmodified controls. These studies will clarify the contribution of epigenetic and genetic modifications to overcoming bacterial defences. Student Ownership:

This project offers multiple avenues for the student to take initiative and shape the work:

Developing new cell-free reaction protocols and optimising production workflows.

Designing novel genetic constructs and testing different anti-defence combinations.

Exploring the impact of specific methylation patterns on phage–host interactions.

Contributing to publications, protocols, and intellectual property emerging from the work.

Collaborative Environment and Training:

The student will be supervised by Westra, Temperton and Szczelkun. We foster a positive research culture that prioritises mutual respect, collegiality, and the highest standards of research integrity. We are dedicated to creating a supportive environment where everyone feels valued and empowered to contribute, and actively promote equality, diversity, and inclusion in recruitment, supervision, and daily practice, recognising that diverse perspectives drive scientific excellence. Our collaborative approach to team science encourages interdisciplinary exchange, shared ownership of ideas, and collective success.

Through this collaboration, the student will gain cutting-edge skills in: Cell-free synthetic biology and phage manufacturing.

Genetic and epigenetic engineering of phage genomes. Microbiological assays and infection modelling.

Genomic and epigenomic characterisation of phage particles.

The student will be embedded in an exceptional network of research activity and expertise through:

1)  the BBSRC-funded sLoLa "MultiDefence" project, led by Prof. Westra, which investigates the mechanisms and evolution of the P. aeruginosa immune system against phage infections (https://sites.exeter.ac.uk/multidefence/).

2)  the Safephage project (led by Mike Brockhurst, Westra co-I), which focuses on the safe and effective development of synthetic phage therapies using a yeast-based rebooting platform and in vivo phage production host.

3)  The Citizen Phage Library project (led by Ben Temperton), which develops bespoke Pseudomonas phage treatments.

Funding

This studentship is funded through GW4BioMed2 MRC Doctoral Training Partnership. It consists of UK tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£20.20780 p.a. for 2025/26, updated each year).

Additional research training and support funding of up to £5,000 per annum is also available.

Eligibility

Residency:

The GW4 BioMed2 MRC DTP studentships are available to UK and International applicants. Following Brexit, the UKRI now classifies EU students as international unless they have rights under the EU Settlement Scheme. The GW4 partners have agreed to cover the difference in costs between home and international tuition fees. This means that international candidates will not be expected to cover this cost and will be fully funded but need to be aware that they will be required to cover the cost of their student visa, healthcare surcharge and other costs of moving to the UK to do a PhD.  All studentships will be competitively awarded and there is a limit to the number of International students that we can accept into our programme (up to 30% cap across our partners per annum).

Academic criteria:

Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences.  Applicants with a lower second class will only be considered if they also have a Master’s degree. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.

English requirements:

If English is not your first language you will need to meet the English language requirements for the University of Exeter by the start of the programme. Please refer to the details in the following web page for further information https://www.exeter.ac.uk/study/englishlanguagerequirements/

Please check the relevant English Language requirements of the university that will host the PhD project.  

Data Protection

If you are applying for a place on a collaborative programme of doctoral training provided by Cardiff University and other universities, research organisations and/or partners please be aware that your personal data will be used and disclosed for the purposes set out below.

Your personal data will always be processed in accordance with the General Data Protection Regulations of 2018. Cardiff University (“University”) will remain a data controller for the personal data it holds, and other universities, research organisations and/or partners (“HEIs”) may also become data controllers for the relevant personal data they receive as a result of their participation in the collaborative programme of doctoral training (“Programme”).

Further Information

For an overview of the MRC GW4 BioMed programme please see the website www.gw4biomed.ac.uk

Entry requirements

Academic Requirements

Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences. Applicants with a lower second class will only be considered if they also have a Master’s degree. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.

English Language Requirements

If English is not your first language you will need to meet the English language requirements for the University of Exeter by the start of the programme. Please refer to the relevant university website for further information.  This will be at least 6.5 in IELTS or an acceptable equivalent.  Please refer to the English Language requirements web page for further information.

Please check the relevant English Language requirements of the university that will host the PhD project. 

How to apply

A list of all the projects and how to apply is available on the DTP’s website at gw4biomed.ac.uk.  You may apply for up to 2 projects and submit one application per candidate only.

Please complete an application to the GW4 BioMed2 MRC DTP for an ‘offer of funding’.  If successful, you will also need to make an application for an 'offer to study' to your chosen institution.

Please complete the online application form linked from our website by 5.00pm on Monday, 20th October 2025.  Please note that we may close the application process before the stated deadline if an unprecedented number of applications are received– check the DTP’s website for details and updates

If you are shortlisted for interview, you will be notified from Tuesday, 23rd December 2025.  Interviews will be held virtually on 27th and 28th January 2026.  

Further Information

For informal enquiries, please contact GW4BioMed@cardiff.ac.uk

For project related queries, please contact the respective supervisors listed on the project descriptions on our website.

Summary