Molecular Biology of Antiviral Signalling in the CRISPR system

CRISPR is a prokaryotic adaptive immune system that has been harnessed for a wide range of genome engineering, synthetic biology, biotechnology and healthcare applications. This project will focus on the Type III CRISPR system which is more complex than Cas9, consisting of a large ribonucleoprotein machine that detects tiny amounts of viral RNA and unleashes an array of defensive enzymes that target and degrade invading genetic entities. In 2017, this system was shown to generate a completely novel type of ring-shaped signalling molecule, cyclic oligoadenylate (cOA). Although this is a powerful immune defence, it must be tightly controlled to avoid killing the host. Recently we showed how the system is controlled in the model organism Sulfolobus solfataricus (Rouillon et al., eLife, 2018) and discovered a novel class of enzymes that degrades the signalling molecule to switch off the antiviral state (Athukoralage et al., Nature 2018).

Many aspects of the Type III CRISPR system remain to be discovered. In this project, you will focus on cellular response to the cOA signalling molecule, which binds to and activates a range of proteins including nucleases and transcription factors. We are working with collaborators in London and the USA to characterise this signalling system both in vitro and in vivo, and there will be possibilities for lab exchanges with our partners.

You will have a degree in the broad area of the Life Sciences and an interest in the molecular biology of the CRISPR system. We will provide opportunities for training in a wide range of cutting-edge technologies including molecular biology, biochemistry and microbiology. You will join a well-funded and friendly lab with good technical support, occupying new, purpose-built lab space in the Biomedical Sciences Research Complex at St Andrews. For more information or informal enquiries, please contact Prof Malcolm White ([Email Address Removed]).