Obiettivo Despite the worldwide growing incidence of type-two diabetes (T2D), the molecular mechanisms are largely unknown. Genome Wide Association Studies (GWAS) have identified dozens of loci harbouring common SNPs that affect T2D susceptibility. The host lab recently showed that many associated SNPs lie in clusters of islet-specific regulatory elements that form tridimensional chromatin structures in the nucleus. This project aims to evaluate how common genetic variation could impact the tridimensional chromatin structure and transcriptional activity at the level of broad regulatory domains, and ultimately assess its influence on T2D risk. To this end, allele-specific chromosome conformation capture maps will be developed and analysed together with existing reference regulatory datasets of expression profiles, histone modification marks and transcription factor occupancy in human islets. To further define the function of allele-specific interactions, genetic modification experiments will be carried out on selected disease-relevant regulatory elements. These studies can shed novel insights on how common sequence variation contributes to T2D susceptibility and can lead to the identification of novel non-coding functional variants. Campo scientifico natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesmedical biotechnologygenetic engineeringmedical and health sciencesclinical medicineendocrinologydiabetesnatural sciencesbiological sciencesgeneticschromosomesmedical and health scienceshealth sciencesnutritionobesity Parole chiave Type-two-diabetes GWAS SNPs long-range interactions tridimensional structure 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 - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinatore FUNDACIO DE RECERCA CLINIC BARCELONA-INSTITUT D INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER Contribution nette de l'UE € 158 121,60 Indirizzo CARRER ROSSELLO 149 08036 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