Resistance to antibiotics (known as antimicrobial resistance) is a growing problem, identified by the World Health Organisation as a top-10 threat facing humanity. This project will investigate the defence mechanisms of bacterial cells, to help stop the spread of drug-resistant genes.
The aim is to uncover defence systems that could be exploited for engineering biology, especially using phages (viruses that infect bacteria). Unpicking the complex interactions among mobile genetic elements, phages, and bacterial defence systems in natural populations is key to understanding antimicrobial resistance dynamics. Our research programme builds on the very recent discovery of a large diversity of defence systems that frequently co-exist in the same cell, where they cluster in ‘defence islands’. Our results will be of key strategic importance for UK healthcare, industry and biotech.We aim to use a wide range of methods to work out how bacterial defence systems shape the evolution of mobile genetic elements (MGEs), which play a key role in spreading antimicrobial resistance.
The project team includes researchers from the universities of Exeter, Cambridge, Durham, Manchester, Bath, Bristol, Liverpool and St Andrews. Our ambitious goal is to tease apart how complex, multi-layered, bacterial immune systems operate at the level of individual molecules, cells, populations and microbial communities. This will require expertise in bioinformatics, molecular microbiology, biochemistry, mathematical modelling, microscopy and experimental evolution techniques – so we have assembled a team of world-leading UK researchers covering all these fields.
The project will combine genomics, modelling and experimental analyses of Pseudomonas aeruginosa bacteria to determine which defences occur together, which interact synergistically, what causes synergy, how the activation of different defences is orchestrated and how they shape bacteria-MGE dynamics. Data from P. aeruginosa will be generalised through genomics analyses across all bacterial taxa and selected experiments with additional taxa to identify general rules of life. This project will apply interdisciplinary thinking and experimental capacity to lay the foundations for an entirely novel area in the field of bacteria-MGE interactions.
The £4.6m, five-year programme has won a grant from the Biotechnology and Biological Sciences Research Council (BBSRC) under the strategic longer and larger grants (sLoLa) scheme.
