Professor Angus Buckling, Department of Biosciences, College of Life and Environmental Sciences, University of Exeter
Dr Ben Ashby, University of Bath
Prof William Gaze, College of Medicine and Health, University of Exeter
Antimicrobial resistance (AMR) can spread through microbial communities via parasites that jump between species, creating complex network of interactions. As such, controlling AMR will benefit from approaches developed for understanding ecological communities and social networks. The project will combine theory and laboratory techniques to do this.
Antimicrobial resistance (AMR) represents one of the most challenging problems facing society today, and novel approaches to mitigate this problem are desperately needed. Antibiotic resistance genes are frequently carried on mobile genetic elements (plasmids) that can spread through entire bacterial communities. Understanding and controlling the spread of resistance in such complex circumstances is difficult. Fortunately, recent years has seen the development of a new field – network ecology – that offers the tools and conceptual framework to achieve this. A key prediction is that where interactions within networks are primarily negative, then species tend to specialise on each other, while beneficial interactions leads to networks where interactions are more generalised. Crucially, antibiotics can shift plasmids carrying resistance genes from being primarily detrimental to their hosts to being very beneficial. This suggests that antibiotic treatment may itself create networks that contain generalist “hub” species that promote the spread of subsequent antibiotic resistance genes throughout microbial communities.
The interdisciplinary project will combine mathematical modelling, experimental evolution and metagenomics to develop and test theory about the interplay between plasmid-bacteria networks and antibiotic pressure. Ashby, a bio-mathematician at Bath will supervise the theoretical work. He has extensive experience modelling host-symbiont dynamics, and has collaborated with Buckling on related questions. The experimental work will be conducted in a model bacteria-plasmid community that Buckling has developed in a complementary NERC grant (2019-2021). We will determine how initially identical bacteria-plasmid networks develop in the presence and absence of antibiotics; how this affects the spread of plasmids to new community members, and the spread of new plasmids introduced into the community; and whether plasmid spread can be mitigated by selectively targeting bacteria. Finally, we will measure bacteria-plasmid networks in natural sewage communities that differ in antibiotic exposure, by carrying out metagenomic analyses of different isolated bacterial taxa. This work will be conducted under the supervision of Gaze (based in the same lab as Buckling), an expert in environmental AMR. The project addresses a key issue in medical research from a unique angle and offers extensive inter-disciplinary training opportunities.
Supervision will be provided by a team of experts with highly complementary skills, excellent research and training track records, and a proven history of collaboration. The project will be based at Exeter’s Penryn campus, but with regular meetings with Ashby, who will also host the student for training in Bath. Impact, and exposure to industry and policy makers, will be realised through Gaze’s NERC Knowledge Exchange Fellowship on AMR in the environment.
To apply for this project, please complete the application form at https://cardiff.onlinesurveys.ac.uk/gw4-biomed-mrc-doctoral-training-partnership-student-appl
by 5pm Friday 25 November 2019.