Objetivo In eukaryotes, silencing small (s)RNAs, including micro (mi)RNAs and small interfering (si)RNAs, regulate many aspects of biology, including cell differentiation, development, hormonal responses, or defense. In particular, many plant and metazoan miRNAs play crucial roles in embryonic/post-embryonic development; the precise timing and localization of their expression is thus crucial to their action. Hence, specific miRNA repertoires underlie specific cell identities, and deviations from such repertoires often have deleterious consequences such as cancer. Many miRNAs also help organisms to adapt to stress, thus, given their importance in virtually all aspects of biology, understanding how, when and where miRNAs exert their actions is of paramount importance. To date, however, the few approaches to miRNA-mediated silencing in whole organisms have not taken into account the exquisite definition, in space and time, of their biogenesis and action, leading to an inaccurate view of the biology of these molecules at the systems level.Using the root system of the model plant Arabidopsis thaliana, we propose to explore, at single-cell and subcellular resolution levels, the biology of the main miRNA effector protein, ARGONAUTE 1 (AGO1) in intact tissues. Using a combination of state-of the-art technologies for single-cell forward genetics, protein purification and RNA/polysome profiling, we will establish a functional spatiotemporal map of the root AGO1-sRNAome and identify cell-specific modifiers of sRNA biogenesis and action. As a complement to the above approaches, chemical genetics will isolate small molecules allowing direct and specific manipulation of AGO1-dependent sRNA pathways in planta. RNA silencing modifier compounds will also accelerate forward and reverse approaches of RNA silencing in plants with sensitized genetic backgrounds, and uncover novel connections between miRNA/siRNA and physiological or metabolic pathways. Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsRNA Programa(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) Tema(s) ERC-AG-LS2 - ERC Advanced Grant - Genetics, Genomics, Bioinformatics and Systems Biology Convocatoria de propuestas ERC-2012-ADG_20120314 Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-AG - ERC Advanced Grant Institución de acogida EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Aportación de la UE € 2 251 600,00 Dirección Raemistrasse 101 8092 Zuerich Suiza Ver en el mapa Región Schweiz/Suisse/Svizzera Zürich Zürich Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Olivier Robert Georges Voinnet (Prof.) Investigador principal Olivier Robert Georges Voinnet (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Suiza Aportación de la UE € 2 251 600,00 Dirección Raemistrasse 101 8092 Zuerich Ver en el mapa Región Schweiz/Suisse/Svizzera Zürich Zürich Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Olivier Robert Georges Voinnet (Prof.) Investigador principal Olivier Robert Georges Voinnet (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
