GW4 BioMed3 MRC DLP PhD project: Co-evolution of bacteriophage within bacterial microbiomes and development of phage therapies

About the project

About the Project This project is one of several in competition for funding from the GW4 BioMed3 MRC Doctoral Landscape Programme (DLP), which is offering up to 17 studentships for entry in September 2027. The partnership brings together the Universities of Bath, Bristol, Cardiff 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. More information may be found on the DLP’s website . Please note that the application process may close early to either home or international candidates (or both) before the stated deadline if an unprecedented number of applications are received – check the DLP’s website for details and updates. Supervisory Team: Dr Brian Jones (University of Bath) Prof Eshwar Mahenthiralingam (University of Cardiff) Prof J Mark Sutton (UKSHA) Prof Tiffany Taylor (University of Bath) Background Antimicrobial resistance (AMR) constitutes a major global threat to public health and without intervention, this crisis is predicted to claim ~10 million lives and cost $1 trillion USD a year by 2050. This has renewed interest in the development of alternatives to antibiotics that could limit the spread of AMR. Viruses that specifically infect and kill bacteria (bacteriophage or phage) are a promising approach to control a range of infections, particularly those associated with indwelling medical devices where biofilm formation is a major problem. Biofilms are surface-associated bacterial communities encased in an extracellular polymeric matrix which affords protection against immune clearance and antibiotic treatment. Phage have evolved mechanisms to penetrate the extracellular matrix and infect biofilm associated cells which could be exploited to develop new treatments for these infections. Our previous work has already highlighted the potential for phage to control catheter associated urinary tract infection (CAUTI) and inhibit biofilm formation on these devices. However, the development and application of effective phage therapies requires a deeper fundamental understanding of factors that modulate the interaction of phage and bacterial hosts. Bacteria predominantly exist within polymicrobial communities (or microbiomes) in many clinically relevant habitats, including infections such as CAUTI. This raises important questions regarding the co-evolution of phage and target species within these communities, how effective phage are at killing target species within a polymicrobial community, and the effect of phage treatment on mobilisation of antibiotic resistance genes within microbiomes. Aims & Objectives Focusing on phage infecting Klebsiella pneumoniae and using a clinically relevant in vitro model of polymicrobial CAUTI, this project will address key questions regarding the co-evolution of bacteriophage and hosts within bacterial communities, and the application of phage to resolve biofilm associated infections. Klebsiella pneumoniae is a prominent opportunistic pathogen, a particular concern in terms of AMR, and forms extensive biofilms on catheter surfaces which incorporate and protect other pathogens. The CAUTI model provides a tractable microbiome system replicating both planktonic and biofilm components, and facilitates the use of directed evolution, genomic, metagenomic, and biochemical approaches to understand community response and validate new therapeutic approaches. Objective 1 - Phage isolation and characterisation. Bacteriophage will be isolated against a panel of K. pneumoniae clinical isolates and characterised in terms of genome composition, capsid structure, host-range, and ability to infect and disrupt K. pneumoniae biofilms. Factors influencing phage host range and infection will initially be explored using directed evolution approaches, comparative genomics, and targeted mutagenesis approaches. Objective 2 - Phage therapy and host-phage co-evolution in polymicrobial communities. Models of CAUTI will be used to evaluate the capacity of individual phage, or phage combinations, to target and eliminate K. pneumoniae alone or when embedded in a bacterial community. This will include analysis of both planktonic and biofilm associated components of these microbiomes, through phenotypic and genomic characterisation of bacterial and viral populations recovered pre and post treatment. Objective 3 - Plasmid transfer and phage defence systems. The transfer of plasmids between bacterial species is a key mechanism in the dissemination of antibiotic resistance, but these mobile genetic elements have also been found to encode defence systems that confer protection against bacteriophage. Therefore, there is potential for target species to rapidly acquire mechanisms that undermine phage therapy and for the application of phage to inadvertently promote the spread of plasmids encoding antibiotic resistance genes. Using our polymicrobial CAUTI model we will investigate the impact of phage exposure on transfer of plasmids between community members. This will include plasmids encoding phage defence systems and antibiotic resistance genes, either alone or in combination. Requirements: Applicants must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences. Applicants with a lower second-class degree will only be considered if they have a grade of Merit or above in a master’s degree. Academic qualifications are considered alongside significant relevant non-academic experience. Non-UK applicants will also be required to have met the English language entry requirements of the University of Bath. Enquiries and Applications: Informal enquiries are welcomed and should be directed to Dr Jones. Formal applications must be submitted direct to the GW4 BioMed3 DLP using their online application form . A list of all the projects and details on how to apply are available DLP’s website . You may apply for up to 2 projects and submit one application per candidate only. APPLICATIONS CLOSE AT 17:00 (GMT) ON 21 OCTOBER 2026. IMPORTANT: You do NOT need to submit a separate application to the University of Bath at this stage. Equality, Diversity and Inclusion: We value a diverse research environment and aim to be an inclusive university, where difference is celebrated and respected. We welcome and encourage applications from under-represented groups. If you have circumstances that you feel we should be aware of that have affected your educational attainment, then please feel free to tell us about it in your application form. The best way to do this is a short paragraph at the end of your personal statement.

Research areas