Grant: Discovery Grants Program - Individual

We study the molecular mechanisms by which plants defend themselves against pathogens in general, and viruses in particular. One of the main defences against plant viruses is based on targeting the RNA genetic material of the virus. A mechanism broadly known as RNA silencing exists in all eukaryotes that recognizes double-stranded RNAs and is responsible for regulating multiple biological processes, including virus resistance by targeting viral double-stranded RNA for degradation. Dicer proteins process double-stranded RNAs into defined small RNAs and these in turn are incorporated into ""slicer"" complexes which target any RNAs with complementarity to the small RNA. The active components of slicer complexes are a family of endoribonucleases known as Argonaute (AGO) proteins. Higher plant genomes encode at least ten AGO proteins, which are involved in a variety of RNA silencing-related phenomenon, and some of these have been implicated in constitutive anti-viral defences. In turn, plant viruses have evolved suppressors of RNA silencing to overcome this constitutive defence. However, in addition to RNA silencing, plants encode immune receptor-like proteins (NB-LRR proteins) that recognize all types of pathogens and induce a dramatic suite of defence responses. We have found that NB-LRR proteins engage certain AGO proteins to occlude viral RNAs from translating protein, hence stopping the virus from spreading. However, this process appears to use different AGOs family members than those involved in constitutive anti-viral responses. We will identify which AGO family members are responsible for both constitutive and induced anti-viral responses and we will characterize how these proteins affect the translation of viral RNA transcripts using a variety of plant model systems, genetics, biochemistry, cell and molecular biology. In addition we will identify cellular proteins that interact with NB-LRR proteins in order to gain more insight into how induced anti-viral responses are initiated.