Different viruses have evolved to produce short or long RNAs that enter host RISCs and impact gene expression. As intracellular obligate parasites, viruses provide unique models to understand how foreign RNAs can enter host RNAi pathways, how the RNAi pathways are regulated and how RNAi signals are transmitted from one cell to another. We are currently studying the viral-host RNA interactions that enable signalling from infected to uninfected cells in herpesvirus and respiratory virus infection.
The mammalian gut is a complex ecosystem of different organisms that communicate to share resources, coordinate digestion and maintain homeostasis. In many animals, parasitic nematodes are part of this ecosystem, where they promote tolerance and modulate the local environment to favour their survival. We have found that gastrointestinal nematodes release both RNA and protein components of RISCs (Argonaute proteins) to modulate host cells and the gut environment. We want to understand how RNA transmission from a nematode to a mammal works and what role RNA communication plays in gut homeostasis, infection and inflammation.
We hypothesize that RNA can be naturally transmitted between mammalian cells as a communication mechanism and pathogens have evolved to exploit this. We are using biochemical and genetic strategies to understand how RISC components (both RNAs and proteins) can be transmitted from one cell to another (inside or outside of extracellular vesicles) in mammals. Ultimately, we want to understand the evolution of RNA-based communication, its function inside organisms, as well as its role in enabling complex multi-organism communities.