The role of the antiviral RNA interference response in the C. elegans–Orsay virus pathosystem

ongoing

Viruses infect all known living organisms, and the RNA interference (RNAi) response is one of the main defense mechanisms cells use against viruses. Even though we have a general understanding of the players involved in the antiviral RNAi response, with some systems more characterized than others, we still lack mechanistic details about the process. For example, in the C. elegans-Orsay virus pathosystem, loss of certain RNAi proteins can be advantageous for the virus, but it is still unclear whether this is because the virus highjacks the RNAi machinery for its own advantage or because the absence of certain RNAi proteins frees up resources which can then be used for antiviral defense. Moreover, preliminary results show that there are distinct viral RNAi silencing complexes, but the composition and function of these complexes is still unknown. Finally, the RNAi response seems to prevent multicellular viral colonization through yet unidentified mechanisms. In this proposal we aim to address these three open questions to improve our understanding of the role of RNAi in the defense response to a viral infection. We will perform a comprehensive analysis of the antiviral RNAi pathway and the Argonautes – the main effectors of the RNAi pathway –, their interactors and targets upon Orsay virus infection. We will use a multidisciplinary approach, combining in-depth analyses from virology, cell biology, genetics, genomics and developmental biology. This will be possible due to the collaboration between the researcher and the laboratories of Prof. Elena, the coordinator and virology expert, and Prof. Claycomb, the outgoing phase host and cell biology and small RNA regulation expert. The expertise the researcher will obtain goes beyond the research in either laboratory and will help her crystalize the unique research profile necessary to take her career to the next level of independence.