Obiettivo Understanding how the differentiation potential of the mammalian embryo gets restricted during development is a key question in the embryology and stem cell fields. Alternative splicing (AS) is the process by which different exons are selected in precursor mRNAs to generate multiple protein products. Recent studies have shown that 95% of human multiexonic genes undergo AS, however little is known regarding its role in modulating pluripotency and differentiation. The aim of this project is to study the role that AS plays in these processes. For this we will first use ultra-deep coverage RNA-sequencing data from three mammalian species to identify alternative exons that show conserved dynamic usage during early developmental stages. Second, we will functionally test in ESCs the role of a number of these isoforms in pluripotency maintenance. Finally, we will take advantage of the CRISPR-Cas9 technology to generate exon specific knockouts in mouse embryos in order to assess their role during early embryo development. The results obtained from the proposed research will add to our knowledge of the regulatory networks that control early embryo development and will improve our understanding of the biology of stem cells, which is essential for their effective use for therapeutic applications. In addition, the use of state-of-the-art technology and a multi-disciplinary approach to analyze mammalian pluripotency regulation will improve my expertise in this field, helping me to gain independence in the near future. Campo scientifico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineobstetricsmedical and health sciencesmedical biotechnologyimplantsmedical and health sciencesclinical medicineembryology Programma(i) 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 Argomento(i) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Invito a presentare proposte H2020-MSCA-IF-2014 Vedi altri progetti per questo bando Meccanismo di finanziamento MSCA-IF-EF-ST - Standard EF Coordinatore FUNDACIO CENTRE DE REGULACIO GENOMICA Contribution nette de l'UE € 158 121,60 Indirizzo CARRER DOCTOR AIGUADER 88 08003 Barcelona Spagna Mostra sulla mappa Regione Este Cataluña Barcelona Tipo di attività Research Organisations 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 € 158 121,60