Objective Viruses are simple, obligatory, intracellular parasites that depend on the host cell for most of the steps in the replication cycle. Not only do they rely on the cells biosynthetic machinery, they exploit cellular processes for signaling, membrane trafficking, intra-cellular transport, nuclear import and export, molecular sorting, transcriptional regulation, etc. To access the full spectrum of host cell functions in the infection of three different viruses in an unbiased and systematic fashion, we will identify the critical host cell proteins needed by monitoring infection in human tissue culture cells after silencing individual genes using genome-wide siRNA libraries and large sub-libraries based on the human genome. The three viruses are vaccinia virus (a poxvirus), human papilloma virus 16, and Uukuniemi virus (a bunyavirus). They are members of important but poorly analyzed pathogen families representing enveloped and nonenveloped viruses, RNA and DNA viruses, viruses that replicate in the nucleus and in the cytosol. The infection assays to be used are fully automated, and make use of high-content microscopic read-outs for infection and virus production. Identification of the viral infectomes , in this way, offers a valuable, new perspective into the complexities of the infection process, and opens wide new areas of basic and applied research. After validation of hits , extensive biochemical and cell biological analysis will be performed on a selected set of host proteins and pathways identified through the infectome analysis. We will determine which steps in the replication cycle are affected, which mechanisms are involved, and which cellular pathways play a role. For detailed analysis, we will focus on mechanisms in entry, uncoating, and early intracellular events. A large spectrum of techniques including live cell imaging and single particle tracking will be used to follow up the screening results with functional and mechanistic studies. Fields of science natural sciencesbiological sciencesmicrobiologyvirologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsRNAmedical and health scienceshealth sciencesinfectious diseasesDNA virusesnatural sciencesbiological sciencesgeneticsgenomes Keywords antiviral agents siRNA virus 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-LS6 - ERC Advanced Grant - Immunity and infection Call for proposal ERC-2008-AdG See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH EU contribution € 2 498 400,00 Address Raemistrasse 101 8092 Zuerich Switzerland See on map Region Schweiz/Suisse/Svizzera Zürich Zürich Activity type Higher or Secondary Education Establishments Principal investigator Ari Helenius (Prof.) Administrative Contact Ari Helenius (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Switzerland EU contribution € 2 498 400,00 Address Raemistrasse 101 8092 Zuerich See on map Region Schweiz/Suisse/Svizzera Zürich Zürich Activity type Higher or Secondary Education Establishments Principal investigator Ari Helenius (Prof.) Administrative Contact Ari Helenius (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
