Obiettivo RNAs are linear biopolymers that consist of only four types of building blocks, but can fold into complex three-dimensional structures that are endowed with selective, high-affinity ligand-binding abilities known as aptamers, and catalytic activities known as ribozymes. Genome projects have brought the surprising insight that a large part of the human genome is transcribed into RNAs, but only a very small fraction is translated into proteins. The actual number of noncoding RNAs with specific functions is currently unknown, but many are considered as prominent regulators of cellular functions. Posttranscriptional modifications of RNA add an extra layer of complexity, but their regulatory roles in RNA metabolism are only poorly understood. Despite the relative simplicity in molecular composition, the available methodological repertoire for manipulation, interrogation and visualization of RNA is rather limited. This project aims to solve the challenge of RNA labeling in both fixed and living cells, using aptamers and ribozymes for RNA imaging and functional characterization. We introduce the term illumizymes for novel tools that attach bio-orthogonal tags and fluorophores to specific RNA sequences, in vitro and in vivo. Ribozymes and aptamers for small, stable, and specific labels will be identified by in vitro selection and systematic evolution of ligands by exponential enrichment (SELEX) to activate the fluorescence of latent chromophores by restricting their conformational flexibility and/or formation of covalent bonds by new bio-orthogonal reactions. Using naturally inspired, cell-permeable and non-toxic ligands, we will specifically select for increased brightness and photostability, and evolve illumizymes into color-switching probes for RNA microscopy. The new genetically encodable RNA devices will find widespread applications in diverse disciplines to enlighten our understanding of cellular RNA functions in health and disease. Campo scientifico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopynatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesgeneticsgenomes Parole chiave RNA DNA bio-orthogonal chemistry nucleoside synthesis solid-phase synthesis aptamer ribozyme in vitro selection SELEX fluorescence RNA labeling sequencing cloning imaging microscopy Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-CoG-2015 - ERC Consolidator Grant Invito a presentare proposte ERC-2015-CoG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-COG - Consolidator Grant Istituzione ospitante JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG Contribution nette de l'UE € 1 977 500,00 Indirizzo SANDERRING 2 97070 Wuerzburg Germania Mostra sulla mappa Regione Bayern Unterfranken Würzburg, Kreisfreie Stadt Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 977 500,00 Beneficiari (2) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG Germania Contribution nette de l'UE € 1 977 500,00 Indirizzo SANDERRING 2 97070 Wuerzburg Mostra sulla mappa Regione Bayern Unterfranken Würzburg, Kreisfreie Stadt Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 977 500,00 GEORG-AUGUST-UNIVERSITAT GOTTINGEN STIFTUNG OFFENTLICHEN RECHTS Partecipazione conclusa Germania Contribution nette de l'UE € 83 750,00 Indirizzo WILHELMSPLATZ 1 37073 Gottingen Mostra sulla mappa Regione Niedersachsen Braunschweig Göttingen Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 83 750,00