Objetivo It has recently become apparent that post-transcriptional editing of mRNA by methylation of adenosines (m6A) plays a key role in regulating gene expression. In particular, total loss of m6A editing blocks the development of early embryos in a number of organisms. However, how m6A modifications, which are added in the nucleus and primarily detected by 3 cytoplasmic “reader” proteins, exert their effects remains unknown. The presence of m6A on viral transcripts has been known for 40 years, yet has only recently been shown to enhance HIV-1 gene expression and replication. Influenza A virus (IAV) that, like HIV-1, replicates in the nucleus, is known to bear a high level of m6A on viral RNA. However, whether and how m6A editing affects IAV replication remains unknown. Here, the researcher proposes the investigation of the role of m6A in IAV pathogenesis. The main objectives of this proposal are; to compile a precise map of m6A sites on IAV-PR8 RNA, determine their functional significance on replication and RNA trafficking, assess how m6A machinery is altered in IAV infected cells, and evaluate the conservation of these sites across additional pathogenic IAV strains.Preliminary data demonstrates that IAV gene expression may be enhanced by overexpression of the m6A reader proteins. Therefore the researcher proposes that IAV may subvert the m6A modification pathway to enhance viral RNA expression. Mapping of m6A modifications will be performed using PAR-CLIP and PA-m6A-seq, while RNAi, CRISPR knockouts and lentiviral overexpression systems will be utilised to determine the functional role of m6A editing on IAV pathogenesis. This fellowship will provide the researcher with an excellent opportunity to work at 2 highly regarded research institutes and advance his knowledge in virology and RNA biology. The skills acquired through completion of this fellowship will greatly assist him in his future endeavours including the establishment of his own European research group. Ámbito científico natural sciencesbiological sciencesmicrobiologyvirologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health scienceshealth sciencesinfectious diseasesRNA virusesinfluenzanatural sciencesbiological sciencesgeneticsRNAmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals Programa(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Tema(s) MSCA-IF-2016 - Individual Fellowships Convocatoria de propuestas H2020-MSCA-IF-2016 Consulte otros proyectos de esta convocatoria Régimen de financiación MSCA-IF-GF - Global Fellowships Coordinador INSTITUT PASTEUR Aportación neta de la UEn € 264 668,40 Dirección RUE DU DOCTEUR ROUX 25-28 75724 Paris Francia Ver en el mapa Región Ile-de-France Ile-de-France Paris Tipo de actividad Research Organisations Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 264 668,40 Socios (1) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo Socio Las organizaciones asociadas contribuyen a la aplicación de la acción, pero no firman el acuerdo de subvención. DUKE UNIVERSITY Estados Unidos Aportación neta de la UEn € 0,00 Dirección ALLEN BUILDING 207 27708 Durham Nc Ver en el mapa Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 172 130,40