Essential virus sensors: investigating RNA receptors in infection

The innate immune system is the body’s first line of defence against infection, and is necessary for our survival. Our cells have evolved specialized mechanisms for sensing viral infection to kickstart an immune response. Sensors of aberrant nucleic acids play a key role in detection of viruses. Among these, receptors that bind double-stranded RNA, such as MDA5, PKR and OASs can detect a wide array of viruses, including SARS-CoV-2, West Nile virus, and Zika. However, the activation and regulation of these receptor signalling pathways are poorly understood. This project will investigate these receptors in the context of important human pathogens, such as in respiratory infections and mosquito-borne viruses, to gain biologically relevant insight into their role in protection from disease. There will be opportunity to apply cutting-edge methods, including next-generation sequencing, iCLIP (Individual-nucleotide resolution UV crosslinking and immunoprecipitation), CRISPR/Cas9 gene editing, and iPSC (induced pluripotent stem cells).