Horizontal transfer of antiviral defences between bacterial species, BBSRC SWBio, PhD in Biosciences studentship (Funded).

The SWBio DTP is one of the 12 Doctoral Training Partnerships funded by the BBSRC to provide PhD training in areas of their strategic relevance. The SWBio DTP is 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. For further details about the programme please see https://www.swbio.ac.uk/

Supervisory team:
Dr Edze Westra, Department of Biosciences, College of Life and Environmental Sciences, University of Exeter
Dr Tiffany Taylor, University of Bath
Dr Tim Rogers, University of Bath

Location: University of Exeter, Penryn Campus, Penryn, Cornwall TR10 9FE

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 CRISPR Cas genes to a new bacterial host. An ability to predictably evolve CRISPRCas gene regulation would be truly groundbreaking, 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, evolution and regulation of CRISPR-Cas systems (Westra, Exeter), genetic rewiring (Taylor, Bath), 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 the Westra lab 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.