The deadline for these funded PhD opportunities has now passed. However, if you are eligible for external funding sources and would like to discuss these or another project aligned with our lab interests please contact Rob in the first instance.

Project 1:

Predicting pathogen evolution: using experimental evolution to understand the impact of phage therapy on Clostridioides difficile 

Dr Ellie Harrison and Dr Rob Fagan

Antimicrobial resistance is one of the greatest challenges facing humanity today. We desperately need new therapeutic options and phage therapy - using viruses that kill bacteria - is widely seen as one such approach. However, in order to avoid repeating the mistakes of the past and ensure phage therapy is used to its full potential, we must develop a deeper understanding of the ecological and evolutionary interactions between phages and their target bacteria. We are focussing on the important human pathogen Clostridioides difficile, which kills more than 2,000 every year in the UK alone. C. difficile is intrinsically resistant to many antibiotics, and thrives in the disrupted gut environment created by antibiotic treatment. For this reason, alternative therapeutics - such as phages - are vital. 

However, C. difficile is a spore forming bacteria - able to form metabolically dormant endospores resistant to harsh environments - and phage infection. Evolutionary theory suggests that sporulation may have dramatic impacts on bacteria-phage dynamics, potentially driving unexpected - and unwanted - consequences for infections. This project will leverage our groups’ expertise in experimental evolution (Harrison) and Clostridial cell biology and genetics (Fagan) to dissect the evolutionary interplay between predator and prey in real time. This work will develop the underpinning understanding necessary to make C. difficile phage therapy viable. Specifically, we will use experimental evolution, combined with genome sequencing and molecular genetics to determine how phage predation affects the efficiency of sporulation and how the ability to sporulate affects phage virulence. 

You will receive broad training in state-of-the-art bacterial genetics, experimental evolution and phage biology. You will join a lab with a history of championing diversity and student independence and be embedded in a wider lab group of microbiologists in the School of Biosciences. 

Project 2:

Mechanism of phage infection in the C. difficile pathogen- towards effective phage therapy

Prof Per Bullough, Dr Rob Fagan and Prof Jamie Hobbs

Increasing resistance to antibiotics is one of the greatest challenges facing humanity today. Clostridioides difficile is the primary cause of antibiotic-associated infections in UK hospitals and antibiotic-induced disruption of the gut microbiota is a prerequisite for infection. Current treatments rely on a small number of antibiotics but these cause further damage to the microbiota and relapse is common. There is an urgent need for species specific therapeutics that can kill C. difficile while sparing the beneficial species of the gut microbiota. Bacteriophage are a promising solution to this tricky problem.

Phage are efficient and specific killers of C. difficile which could be further refined through guided genetic engineering. We have developed a streamlined CryoEM pipeline for the structural and mechanistic analysis of phage and have already solved the near atomic resolution structures of two complete contractile phages and one phage tail-like particle that kill C. difficile. We have also shown that the S-layer is the major receptor for the majority of C. difficile phage and have solved the structure of this cell surface structure.In this project we aim to use cutting edge imaging techniques and the insights gained from our structural analyses to study the interaction between the phage and a live cell that leads to successful infection and death of the host cell, at unprecedented resolution.

You will receive training in advanced techniques including super-resolution light microscopy, atomic force microscopy and cryo-electron tomography, supported by three dynamic research groups with a long-established and successful history of collaboration over 11 years, four jointly supervised PhD students and three joint postdoctoral scientists.

EMBO provide funding for 2 year fellowships for internationally mobile candidates. See the EMBO webpage for more information and get in touch with Rob if you'd like to discuss a possible application.

Very similar to the EMBO fellowships above, the Marie Skłodowska-Curie fellowships support postdocs moving within Europe (including the UK) for 1-2 years. The 2025 round will be opening soon, with a deadline in September. If you are interested in exploring a potential collaboration with us for your fellowship please get in touch with Rob.