Objective RNA interference (RNAi) is a conserved sequence-specific, gene-silencing mechanism that is induced by double-stranded RNA (dsRNA). One of the functions of this pathway is the defense against parasitic nucleic acids: transposons and viruses. Previous results demonstrated that viral infections in Drosophila melanogaster are fought by an antiviral RNAi response and that components of the endocytic pathway are required for dsRNA entry to initiate the RNAi response. Recently we have shown that infected insect cells spread a systemic silencing signal that elicits a protective RNAi-dependent immunity throughout the organism. This suggests that the cell-autonomous RNAi response is insufficient to control a viral infection and that flies also rely on systemic immune response to fight against such infections. As a junior group leader, I will study the mechanisms that mediate the RNAi-based antiviral response in insects. By combining biochemical, cellular, molecular and genomic approaches, both in vivo and in cell culture, I will analyze the mechanisms underlying viral tropism, systemic propagation of the antiviral signal and the basis of the persistence of the antiviral state. Furthermore, I will examine whether the dsRNA-uptake pathway is conserved in mosquitoes and its relationship with viral immunity in that host. This comprehensive approach will tackle how this nucleic acid-based immunity works in insects to generate an anti-viral stage. A better understanding of the role of RNA silencing in insects during virus infection will allow the exploitation of this pathway for improvement of public health related problems such as arbovirus infection and disease. Fields of science natural sciencesbiological sciencesmicrobiologyvirologymedical and health sciencesbasic medicineimmunologynatural sciencesbiological scienceszoologyentomologynatural sciencesbiological sciencesgeneticsRNAmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals Keywords RNA silencing antiviral mechanism small RNAs 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-SG-LS6 - ERC Starting Grant - Immunity and infection Call for proposal ERC-2009-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution INSTITUT PASTEUR EU contribution € 1 900 000,00 Address RUE DU DOCTEUR ROUX 25-28 75724 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Principal investigator Maria-Carla Saleh (Dr.) Administrative Contact Marie-Laure Rosso (Ms.) 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 INSTITUT PASTEUR France EU contribution € 1 900 000,00 Address RUE DU DOCTEUR ROUX 25-28 75724 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Principal investigator Maria-Carla Saleh (Dr.) Administrative Contact Marie-Laure Rosso (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
