Grant: Discovery Grants Program - Individual

My research program focuses on studying how the cells are able to make RNA by studying how RNA viruses hijack and disrupt this process. My laboratory has been studying the hepatitis delta virus (HDV) and the influenza A virus (IAV), both have the uncommon trait for RNA viruses of replicating within the nucleus of the host cell and transcribing their RNAs by recruiting RNA polymerase II (RNAP II), one of the main enzymes involved in RNA synthesis. In addition, we have preliminary results suggesting that these viruses could use and disrupt promoter-proximal pausing, a critical step in RNA synthesis and regulation of stimulus-responsive genes by RNAP II. To understand how HDV and IAV hijack and disrupt RNAP II, my research program will use four integrative approaches combining Molecular Biology, Evolution Genetics, and Bioinformatics to: 1) Define the features of HDV RNA structure bound and used by RNAP II 2) Define the features of IAV RNA structure used for RNAP II association 3) Investigate the involvement of RNAP II promoter-proximal pausing in both HDV and IAV transcription 4) Study the disruption of RNAP II promoter-proximal pausing by the only HDV encoded protein. By integrating these approaches, this multidisciplinary research program will allow to understand the biology of these unique RNA-based life forms and will contribute substantially to the understanding of cellular RNA metabolism. These findings and approaches will also be valuable for comprehensive investigations of RNA-protein interactions in other biological processes, and will have broad implications for studying the structure-function relationships of RNA molecules. Furthermore, the requested funding will provide an excellent environment to train new scientists with multidisciplinary skills related to RNA-protein interactions and RNA structure/function relationships using a wide range of molecular biology and bioinformatics techniques, and also produce HQP exceptional at an international level and highly sought by biotechnological, pharmaceutical, diagnostical companies.