RNACOM examines how parasitic worms use small ribonucleic acids (sRNAs) to directly manipulate gene expression in mammalian (host) cells and investigates ways to block or disrupt RNA transmission as a pathogen control strategy. Parasitic worms infect more than a quarter of the human population and are highly prevalent in livestock, ranking first in terms of the global health burden of the neglected tropical diseases and causing substantial economic burdens in Europe. RNACOM builds on our recent discovery of a specific Argonaute protein that gastrointestinal nematodes use to shuttle their RNAs to host cells to change the gut environment and enable parasite survival. The first objective is to capture this protein with antibodies and identify the host genes that are targeted by parasite RNA-induced silencing complexes (RISCs) during chronic infection. We will then determine the specific cells the parasites RISCs enter and examine how they change the host epithelium to allow parasite survival. Finally we use synthetic and recombinant strategies to learn exactly how parasite RISCs cause gene silencing and build on this knowledge to develop new strategies to block RNA transmission by the parasite to treat or control infections.
RNACOM will bring key quantitative and molecular understanding to the processes by which RNA from one species can influence another. The knowledge gained in the gastrointestinal models could illuminate mechanisms used by other pathogens infecting animals and plants that impact health and agriculture. Studying how parasites can effectively deliver their RNAs to mammalian cells could also illuminate new strategies for RNA drug delivery relevant to a range of human diseases.
