The overall aim of this Odysseus proposal is to determine the biological function of Z-RNA in the induction and modulation of the antiviral immune response. I propose to do so by investigating the roles of the only two mammalian Z-RNA binding proteins; ZBP1 (Aim I) and ADAR1 (Aim II). We will interrogate the functionality of ZBP1 and ADAR1 in vivo using mouse models in which Z-RNA binding to these proteins is specifically abrogated. Furthermore, we will determine their RNA interaction partners. Finally, we will develop a tool to track and visualise Z-RNA formation in living cells based on the nanobody technology (Aim III).