RNA functions in parasite-host communication in the gut

Cross-species communication is required for proper functioning of the mammalian gut, where different organisms share resources, coordinate digestion and maintain homeostasis. In many animals, parasitic worms (helminths) are part of this ecosystem, where they communicate through the release of bio-active molecules that promote immunological tolerance and modulate gut functions. Mechanisms of cross-species communication are still not well understood and my lab discovered that ribonucleic acids (RNA) are one of the products helminths release to directly influence host cells. The overall goal of RNACOM is to determine how gastrointestinal parasites use this novel form of RNA communication to regulate the gut epithelium and to develop strategies to block the communication mechanism during infection. We have recently discovered a specific Argonaute protein that gastrointestinal nematodes use to transmit parasite RNAs to mouse cells. We will target this protein to identify parasite-host RNA-RNA interactions that occur during chronic infection (Aim 1). We will then determine the specificity and function of parasite RNA transmission to mouse cells in the epithelium using model organoids and in vivo imaging (Aim 2) and will determine the mechanism of action of parasite RNAs in host gene suppression using synthetic and recombinant strategies (Aim 3). Finally we use genetic tools in the mouse model to determine the function of cross-species RNA-RNA interactions during infection, while testing new strategies to block RNA transmission by the parasite (Aim 4). RNACOM will bring key quantitative and molecular understanding to the processes by which RNA from one species can influence another, advancing a frontier area in RNA biology while testing new strategies of parasite control. In parallel RNACOM develops a unique platform for identifying new gene networks that underpin intestinal cell functions and gut health.