Investigating cyclic nucleotide based anti-viral defence systems in bacteria

1. All living things are subject to attack by viruses. Cells have evolved many different immune systems to protect themselves, including the adaptive and innate immune systems of vertebrates and the CRISPR and restriction:modification systems of bacteria. Viruses have developed potent countermeasures to subvert these systems, and this perpetual arms race has been a strong driving force in evolution throughout the history of life on Earth. Type III CRISPR systems confer a complex, multi-layered defence against viruses. Detection of foreign RNA leads the Cas10 subunit of type III systems to generate the second messenger cyclic oligoadenylate (cOA), which sculpts the cellular response to infection. cOA activates a range of effector proteins, including the NucC nuclease which degrades double stranded DNA on activation, leading to cell death. NucC is associated with both type III CRISPR and CBASS (cyclic-oligonucleotide-based anti-phage signalling systems) defence. This project will focus on the links between CRISPR and CBASS defence systems, which both fight viral infection using cyclic nucleotide second messengers, with a particular emphasis on the effector proteins that bind cOA molecules and effect defence.