Objetivo Throughout evolution, the human genome has been attacked by retrotransposons, parasitic DNA elements that spread through our genome by a copy-paste activity. I previously showed that SVA elements, the youngest class of retrotransposons in our genome, harbour a strong gene-regulatory potential which is normally repressed by KRAB zinc finger protein ZNF91 (Jacobs et al., 2014, Nature). However, for reasons unknown, repression of retrotransposons is much less efficient in the human brain, resulting in activation of the enhancer potential of SVA elements spread throughout the human genome. The importance of these SVA insertions for the evolution of human neuronal gene-regulatory networks, and how many genes have come to depend on SVA's regulatory influence, remains elusive. In this research program, I will use ‘cortical organoids’; three-dimensional brain tissues derived from human and primate stem cells, to investigate how recent SVA insertions have impacted human neuronal gene expression. Furthermore, I will investigate how changes of the epigenetic landscape in neurons affect the activity of retrotransposons in our genome and the influence they have on nearby neuronal genes. Finally, I will explore the possibility that loss of epigenetic silencing of retrotransposons is responsible for dysregulation of genes associated with neurological diseases. Preliminary findings suggest a potential role for retrotransposons in susceptibility loci for Alzheimer's and Parkinson's disease. Finding further support for this in the current research program, will form the basis of a novel concept which explains how changes in the epigenetic landscape can uncover a dormant genetic predisposition to disease. Ámbito científico medical and health sciencesbasic medicineneurologydementiaalzheimermedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesbasic medicineneurologyparkinsonnatural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesgeneticsepigenetics Palabras clave retrotransposons Programa(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Tema(s) ERC-2016-STG - ERC Starting Grant Convocatoria de propuestas ERC-2016-STG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-STG - Starting Grant Institución de acogida UNIVERSITEIT VAN AMSTERDAM Aportación neta de la UEn € 1 500 000,00 Dirección SPUI 21 1012WX Amsterdam Países Bajos Ver en el mapa Región West-Nederland Noord-Holland Groot-Amsterdam Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 1 500 000,00 Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo UNIVERSITEIT VAN AMSTERDAM Países Bajos Aportación neta de la UEn € 1 500 000,00 Dirección SPUI 21 1012WX Amsterdam Ver en el mapa Región West-Nederland Noord-Holland Groot-Amsterdam Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 1 500 000,00
