GBM Lunch

Malcolm F. White: Life, death and cyclic nucleotides: how prokaryotes fight viral infection


Malcolm White


Speaker: Malcolm F. White, Biomedical Sciences Research Complex, School of Biology, St Andrews University, UK

Chair: Lukas Rösner, Institut für Biochemie, Westfälische Wilhelms-Universität Münster

Organizers: Junior GBM

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. The CRISPR system is an adaptive immune system in prokaryotes and consists of six different Types. The discovery of the Cas9 enzyme ( a Type II CRISPR system) was recognised by the award of the Nobel Prize for Chemistry in 2020.  Type III CRISPR systems are much more complicated and less well understood, but provide a 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 ribonuclease Csm6/Csx1, which degrades RNA non-specifically to slow down both viral and host metabolism and “buy some time”. Some organisms encode a dedicated “Ring nuclease” which degrades the cOA signal and returns cells to an uninfected state following viral RNA clearance. This presentation will explore the mechanisms and diversity of cOA-activated effector proteins, and viral counter-measures, in type III CRISPR systems from bacteria and archaea, and links with equivalent innate immune pathways in humans.