PhD Studentship: Horizontal Transfer of Antiviral Defences Between Bacterial Species (BBSRC Funded)

University of Exeter - College of Life and Environmental Sciences

The South West Biosciences Doctoral Training Partnership (SWBio DTP) is a BBSRC-funded PhD training programme in the biosciences, delivered by a consortium comprising the Universities of Bristol (lead), Bath, Cardiff, Exeter, and Rothamsted Research. Together, these institutions present a distinctive cadre of bioscience research staff and students with established international, national and regional networks and widely recognised research excellence. The partnership has a strong track record in advancing knowledge through high quality research and teaching in partnership with industry and government.

This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP).  Up to 4 fully-funded studentships are being offered to start in September 2018 at the University of Exeter.

Academic Supervisors:

Main supervisor: Dr Edze Westra

Co-supervisor: Dr Tiffany Taylor

Co-supervisor: Prof Angus Buckling

Co-supervisor: Dr Tim Rogers

Collaborator: Dr Peter Fineran

Project description:

The discovery of CRISPR-Cas has arguably been one of the most influential discoveries in biology of the past decades. The key finding that CRISPR-Cas systems that are encoded on bacterial genomes protect against viral and plasmid infections is now widely utilised to protect industrial fermentations, and has recently been exploited to eradicate antimicrobial resistance plasmids from microbial communities under laboratory conditions. Furthermore, the recent development of CRISPR-Cas genome editing is facilitating ground-breaking strategies in science, agriculture, medicine and pest management, such as synthetic gene drives to eradicate disease vectors. These examples highlight some of the most significant economic and health impacts that CRISPR-Cas-based technologies are already generating, and further technological advances continue to be developed at a high pace based on expression of CRISPR-Cas systems in bacteria and eukaryotes. However, many of these applications, such as those where CRISPR-Cas are used to protect fermentations or to eradicate antimicrobial resistance, require that the genes encoding CRISPR-Cas are stably expressed across many generations. Yet, long-term studies that examine genetic and transcriptomic stability of these systems are lacking.

This project will address this key gap in our knowledge, using a combination of experimental evolution, molecular genetics, synthetic biology and network modelling. Based on classical evolutionary theory, we hypothesise that we can predictably manipulate the way CRISPR-Cas gene regulation evolves in bacteria following the synthetic or natural transfer of CRISPRCas genes to a new bacterial host. An ability to predictably evolve CRISPR-Cas gene regulation would be truly ground-breaking, and would have clear implications for the use of these systems in industry and in the development of strategies for eradicating antimicrobial resistance.

The project will benefit from expertise in the mechanism and regulation of CRISPRCas systems (Westra, Exeter), genetic rewiring (Taylor, Bath), bacteria-phage coevolution (Buckling, Exeter) and network modelling (Rogers, Bath). Throughout this interdisciplinary project, the student will receive extensive training in experimental evolution, biochemistry, molecular microbiology, genetics and modelling. The student will be part of both the Westra and Buckling labs at the Environment and Sustainability Institute at the Cornwall campus of the University of Exeter (currently 5 PhD and 5 postdoctoral researchers), and the labs of Taylor and Rogers at the University of Bath.

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South West England