GW4 BioMed2 MRC DTP PhD project: Using AI to understand defence and counter-defence systems between bacteria and phage

This project is one of a number that are in competition for funding from the GW4 BioMed2 MRC Doctoral Training Partnership which is offering up to 21 studentships for entry in September 2025.

The DTP 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 DTP’s website.

Supervisory Team:

Professor Zamin Iqbal, University of Bath, Department of Life Sciences (zi245@bath.ac.uk)

Professor Stineke Van Houte, University of Exeter, CEC, ESI

Professor Edze Westra, University of Exeter, CEC, ESI

The Project:

This project aims to apply statistical and AI methods to study one of the most rapidly developing fields in modern biology – the study of how bacteria defend themselves against the viruses that infect them (“phage”), and how phage in turn counteract those defences. The co-supervisors combine expertise in bacterial genomics, bioinformatics, big data, mathematics (Iqbal, Bath)[refs 1,2,3] and bacteria/phage interactions, high throughput phenotyping, defence and anti-defence systems (van Houte, Westra, Exeter) [refs 4,5,6] and are already equipped with extremely rich datasets for analysis. This is an opportunity, thanks to the unique datasets, rapid innovation in modern AI methods, and great expertise within the teams within which the student would be embedded, to make real discoveries impacting both our understanding of fundamental biology, and the development of phage therapy.

Background: The simplest way for bacteria to become resistant to phage is by mutation of the cell surface receptor that phage use to attach to the cell. However, mutation of these receptors is often associated with significant fitness costs, as receptors carry out important cellular functions. An alternative strategy to resist phage is through cellular “immune systems” that act inside bacterial cells to clear infections. Probably the best-known bacterial immune systems are Restriction-Modification (RM) and CRISPR-Cas. Bacteria can also trigger dormancy/cell death upon infection to prevent mobile genetic element (MGE) replication. Literally dozens of previously unknown defence systems have been discovered in recent years, often aided by their clustering in defence-islands. The first systematic study led to the discovery of 9 new families of antiviral defence and a novel family of anti-plasmid defences. A subsequent study identified a further 29 antiviral cassettes that are present in approximately a third of all bacterial genomes. Using similar approaches, a vast diversity of bacterial defences has been revealed. These defences act at different stages of the MGE lifecycle: some cleave MGE genomes immediately following infection, others interfere with MGE transcription or replication or induce cell death or dormancy responses. These diverse defence systems frequently coexist in the same genome and it has been hypothesised that bacterial defence systems consist of multiple integrated layers that act in concert to constrain MGE infections, by providing broader spectrum or higher levels of defence than single systems. In response to the evolution of bacterial immune systems, phages have evolved an equally diverse set of anti-defence systems (ADS). ADSs can counteract bacterial defense systems by modifying the target of the bacterial defence system, interference with the activation of bacterial defenses, inhibition of defence surveillance and effector proteins or by alleviating the impact of programmed cell death or dormancy induction. Crucially, while DS and ADS are very common in bacterial and phage genomes, we lack a fundamental understanding how important they are relative to receptor mutation and relative to one another.

Aims: This project will focus on the opportunistic pathogen Pseudomonas aeruginosa, which causes lung infections in cystic fibrosis patients and immunocompromised people, as well as a range of other infections in healthy people. The Van Houte and Westra labs at Exeter have a collection of >2000 P. aeruginosa isolates and >150 P. aeruginosa-specific bacteriophages. The team has already set up a workflow for high-throughput phage infection experiments and the entire isolate collection is being used to generate large infection datasets that will feed into this PhD project.

Key aims: 1. Identifying host receptors for specific phage via classical statistical approaches (Genome-Wide Association Studies, GWAS) applied to infection data (few phage, many bacteria) 2. Identifying anti-defence systems via GWAS (many phage, few bacteria) 3. Developing AI systems which incorporate both host and virus genomic data to predict susceptibility and use them to explore the biology of host-viral interactions. These aims combine well-understood classical statistical approaches (GWAS) which leverage the unique dataset, with cutting edge new artificial intelligence architectures, which provide a completely orthogonal approach to try to learn the properties of the data. This is a very interdisciplinary project, which would suit someone with data science strengths interested in using it to decipher new biology, or someone with evolutionary and microbiological experience who is keen to engage deeply with new statistical/AI methods.

Requirements:

Applicants must have obtained, or be expected to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an area appropriate to the skills requirements of the project. Applicants with a lower second class will only be considered if they also have 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 Professor Zamin Iqbal – zi245@bath.ac.uk

Formal applications must be submitted direct to the GW4 BioMed2 DTP using their online application form: GW4 BioMed MRC DTP – GW4 BioMed MRC DTP

A list of all available projects and guidance on how to apply may be found on the DTP’s website. You may apply for up to 2 projects.

APPLICATIONS CLOSE AT 17:00 (GMT) ON 4 NOVEMBER 2025.

IMPORTANT: You do NOT need to apply to the University of Bath at this stage – only those applicants who are successful in obtaining an offer of funding from the DTP will be required to submit an application for an offer of study from Bath.