RNA is one of the fundamental building blocks of all living organisms including viruses, plants and animals. Viral genomes produce large amounts of an aberrant form of RNA termed double-stranded RNA during viral replication that our cells have evolved to efficiently recognise, which mounts an early inflammatory response to fight infection. However, our own cells also produce this aberrant RNA during normal cellular functions, so we need effective mechanisms to distinguish this “self” RNA from “foreign” to prevent immune responses against our own RNA. Failure of this self/non-self-recognition results in chronic sterile inflammation.
Our lab studies how cells recognise and regulate double-stranded RNA, how this self/non-self decision is made, and what happens when it fails. We work on the RNA-editing enzymes that mark cellular dsRNA as “self”, on the innate immune sensors that decide whether a given dsRNA species triggers an immune response, and on a growing set of RNA-binding proteins that shape what dsRNA is made, where it goes, and how long it lasts.
This biology has direct consequences for human disease. Inherited variants in the regulators of dsRNA cause the rare childhood dementia, Aicardi-Goutieres Syndrome, in which the dsRNA-sensing pathway is locked in the “on” position. The same self/non-self machinery determines how the body responds to mRNA-based medicines and contributes to inflammation in a broader set of conditions.
