Cel Several human pancreatic diseases have been characterized, being the diabetes the most common. Like others, this genetic disease is related to disrupted non-coding cis-regulatory elements (CREs) that culminate in altered gene expression. Although Genome Wide Association Studies support this hypothesis, it’s still unclear how mutations on CREs contribute to disease. The translation from the “non-coding code” to phenotype is an exciting and unexplored field that we will approach in this project with the help of the zebrafish as a suitable animal model. We aim to uncover the implications of the disruption of pancreas CREs and how they contribute to diabetes in vivo. For this we will study transcriptional regulation of genes in zebrafish. The similarities between zebrafish and mammal pancreas and the evolutionary conservation of pancreas transcription factors (TF) make it an excellent model to approach and study this disease. In this project we will characterize the zebrafish insulin producing beta-cell regulome, by determining the active CREs in this cell type and their bound TFs. Then we will compare this information with a similar dataset recently available for human beta-cells, to define functional orthologs in these species. Selected CREs will be tested by in vivo gene reporter assays in zebrafish, focusing on those functionally equivalent to human CREs where risk alleles have been associated with diabetes or those regulating genes involved in diabetes. Later these CREs will be mutated in the zebrafish genome to validate their contribution to diabetes. Finally we will translate this to predict new human disease-associated CREs by focusing on the regulatory landscape of diabetes-associated genes, without the need of having countless patients to uncover them. With this project we will create a model system that will allow the identification of new diabetes-associated CREs, which might have a great impact in clinical management of this epidemic disease. Dziedzina nauki medical and health sciencesclinical medicineendocrinologydiabetesnatural sciencesbiological sciencesgeneticsgenomes Program(-y) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Temat(-y) ERC-StG-2015 - ERC Starting Grant Zaproszenie do składania wniosków ERC-2015-STG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-STG - Starting Grant Instytucja przyjmująca INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR-IBMC Wkład UE netto € 1 497 520,00 Adres RUA ALFREDO ALLEN 208 4200 135 Porto Portugalia Zobacz na mapie Region Continente Norte Área Metropolitana do Porto Rodzaj działalności Research Organisations Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 497 520,00 Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE netto Rozwiń wszystko Zwiń wszystko INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR-IBMC Portugalia Wkład UE netto € 1 497 520,00 Adres RUA ALFREDO ALLEN 208 4200 135 Porto Zobacz na mapie Region Continente Norte Área Metropolitana do Porto Rodzaj działalności Research Organisations Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 497 520,00
