Selection and evolution of phage-encoded anti-CRISPR genes

ended

CRISPR-Cas immune systems protect bacteria against their viruses (phage). However, some phages encode anti-CRISPR (Acr) genes that block CRISPR-Cas activity. While the molecular understanding of Acr activities and structures are racing ahead, their impact on the ecology and evolution of phage/bacteria populations remains unexplored. I first aim to identify the ecological factors that influence the selection for Acr genes, to explain why some phages encode many Acr whereas most encode none. Next, by running long-term co-culture experiments, I will examine whether CRISPR-Cas can evolve to escape Acr inhibition and whether Acr genes can reciprocally adapt to restore activity. These experiments will reveal how CRISPR-Cas and Acr coevolve and allow to mathematically predict the long-term stability of Acr activity. I will also explore the genetic bases of this coevolution through deep-sequencing analyses. This multidisciplinary project combines my expertise in phage biology, that of the host in experimental evolution and bioinformatics and that of collaborator in mathematical modelling. It is expected to open new avenues of research for downstream medical and bioengineering applications. This high-quality 'training-through-research' will allow me to widen my scientific expertise, develop essential complementary skills and constitute an international collaborative network. The visibility and impact of this research will be increased by a strong dissemination and communication plan. I also aim to reinforce my public engagement activities with a dual objective of making science accessible for everyone and inform about phage research. Carrying out this project within the Centre for Ecology and Conservation at the University of Exeter (EU accredited), a top department in ecology and evolution worldwide, and under the supervision of two world leading scientists in their fields, will be crucial for the development of my career as an independent European researcher.