Objective RNA viruses infect cells to replicate and repackage their genomes in progeny virions. In response, the cellular innate immune system detects viral RNA and triggers powerful anti-viral countermeasures. This proposal aims to elucidate atomic resolution molecular mechanisms associated with these conflicting interests, and will address the following questions: firstly, how do RNA polymerases of segmented, negative sense, single-stranded RNA viruses such as influenza and bunyaviruses transcribe and replicate viral RNA and secondly, how do RIG-I like helicases, intracellular, innate immune, pattern recognition receptors, selectively detect RNA only of viral origin, thus triggering interferon production and induction of the anti-viral state? A third, more exploratory part of the proposal will use proteomics analysis to identify all host factors that are bound to viral mRNAs in influenza virus infected cells. The interdisciplinary project will combine state-of-the-art structural biology with cell-based functional assays and global analysis. Results will advance fundamental understanding of polymerases and helicases, both complex RNA-dependent molecular machines, give new insight into the regulation of innate immune receptor activation and signalling, and shed new light on RNA metabolism in the perturbed environment of the infected cell. They will also impact virology and public health by bringing new knowledge on RNA virus-host interactions, virus evolution and inter-species transmission. More pragmatically the project will boost structure-based anti-viral drug development targeting serious and/or emerging human pathogens such as influenza A, which poses the perennial threat of a devastating pandemic, and the many disease causing bunyaviruses, which in a globally warming world could spread unpredictably. The V-RNA project thus forms a coherent whole covering important protagonists in the virus-versus-host-versus-virus molecular warfare centered around viral RNA. Fields of science natural sciencesbiological sciencesmicrobiologyvirologymedical and health scienceshealth sciencesinfectious diseasesRNA virusesinfluenzamedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticsRNAmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS1 - ERC Advanced Grant - Molecular and Structural Biology and Biochemistry Call for proposal ERC-2012-ADG_20120314 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Coordinator EUROPEAN MOLECULAR BIOLOGY LABORATORY Address Meyerhofstrasse 1 69117 Heidelberg Germany See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Principal investigator Stephen Anthony Cusack (Dr.) Administrative Contact Danielle Desravines (Dr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all EUROPEAN MOLECULAR BIOLOGY LABORATORY Germany EU contribution € 2 371 934,00 Address Meyerhofstrasse 1 69117 Heidelberg See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Principal investigator Stephen Anthony Cusack (Dr.) Administrative Contact Danielle Desravines (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
