Grant: Discovery Grants Program - Individual

Viruses that contain RNA genomes represent a serious threat to the health of plants and animals. Our research program investigates fundamental steps in the reproductive cycle of this type of infectious agent. Our laboratory focuses on the area of RNA-based regulation - the mechanisms by which regulatory RNA elements within viral RNA genomes control critical steps in the infectious process. We study members of the plant virus family Tombusviridae, which are small spherical viruses that contain single-stranded, plus-sensed (i.e. messenger-sensed) RNA genomes. Many viruses in this group cause diseases in a variety of important crop plants. Our research focuses on two members of this virus family, Tomato bushy stunt virus (TBSV) and Red clover necrotic mosaic virus (RCNMV), which are excellent model viruses for understanding the infectious process at the molecular level. The long-term objective of our research program is to understand how these RNA viruses utilize local and global RNA structures to control various steps in their reproductive cycles. In this granting period our short-term goals include: (1) Investigating how the 5'-terminus of an uncapped viral RNA genome resists nuclease attack (2) Understanding how viral RNA genomes fold into conformations that control their gene expression (3) Identifying cellular proteins that bind to viral RNA elements and promote viral genome replication (4) Determining the global architecture of a viral RNA genome that consists of two RNA segments To address these questions, we will use different methods, including computational, biochemical, structural, molecular, and cellular techniques. The results derived from these studies will allow us to better comprehend how these viruses use their RNA genomes to control the infectious process. Understanding RNA-based regulation is important for several reasons. First, it represents a fundamental and distinctive type of regulatory strategy used by many RNA viruses, so our results will likely be relevant to other RNA viruses, and possibly even cellular mRNAs. Second, our work in this field has helped to promote the novel concept that, in addition to local RNA elements, the overall architecture of viral RNA genomes is also important for controlling viral processes. Third, knowledge of RNA-based virus regulation has potential beneficial applications in biotechnology; e.g. through the development of novel antiviral strategies that target and inhibit the activity of viral RNA elements or by modifying their activities in, for example, virus-based protein expression vectors, so as to improve their efficiencies.