Prophages are parasitic genetic elements that integrate within the genomes of bacterial hosts, bursting out with deadly effects in response to stress. Intriguingly, host bacteria can co-opt these dormant viruses into anti-competitor weapons called tailocins (aka ‘Zombie’ phage), thereby transforming parasites into potential assets. This ‘domestication’ process is predicted to strongly influence the course of bacterial infections since both prophages and tailoring enable ESKAPE pathogens like P. aeruginosa (Pa) to outcompete co-infecting rival strains.
In this project, the student will combine bioinformatic, synthetic biology and modelling approaches to study putative phages and tailocins, and their interactions with sequenced clinical Pa isolates. The project comprises 4 main objectives:
- Map prophage & tailocin diversity. The student will use our comparative genomics toolkits to characterise prophage and tailocin gene clusters within Pa genomes.
- Synthesise phage-like elements. The student will use the Cai lab’s YeastFab / cell-free expression platforms to reconstruct putative phages and tailocins.
- Characterise phage and tailocin interactions. Using i) robot-assisted screens and ii) confocal microscopy, we will classify reconstructed elements’ behaviour: are they viruses, tailocins, or something else?
- Predict interactions using machine learning and simulations. The student will use machine learning frameworks to predict phage-like elements’ function from their genotype, and develop agent-based models to understand transitions between these functions in microbial communities.
The student will become a joint member of two flourishing UoM research communities: the Manchester Microbial Evolution Research (MERMan) group, and the Manchester Institute for Biotechnology (MIB)
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