Descripción del proyecto
Dilucidar los mecanismos moleculares de las cromatinopatías
La cromatina es una combinación de ADN y proteínas que forma los cromosomas en los organismos superiores. Las cromatinopatías son un grupo de enfermedades genéticas raras relacionadas con modificaciones en la expresión de los genes debido a cambios genéticos en los reguladores de la cromatina. Se han identificado los genes implicados, pero no se conocen los mecanismos asociados a su inactivación. El equipo del proyecto Chrom rare, que cuenta con el apoyo de las Acciones Marie Skłodowska-Curie, establecerá una red de doctorado para formar a la próxima generación de científicos en los conocimientos y habilidades necesarios para caracterizar las bases moleculares de las cromatinopatías. Al mismo tiempo, la red desarrollará métodos innovadores para traducir los conocimientos moleculares en nuevos métodos diagnósticos y terapéuticos para los pacientes con cromatinopatías.
Objetivo
Chromatinopathies (CPs) are a group of rare genetic diseases, which share clinical features as well as causal genetic alterations, leading to the inactivation of chromatin regulators involved in gene expression control and 3D chromatin organization. Within the framework of Chrom_Rare, we will focus on a group of clinically well-defined CPs, including Kabuki Syndrome, Charge Syndrome, Rubinstein-Taybi Syndrome and Cornelia de Lange Syndrome. Although the causative genes for these CPs have been identified, the consequences of their inactivation both at the molecular and functional level, have not been defined. The clinical features of CPs vary widely, suggesting that the impact of the haploinsufficiency of the affected chromatin regulators could depend on the epigenetic state and/or interactions with additional genetic and environmental factors. Hence understanding the genetic and epigenetic determinants of CPs represent an immediate medical need, as this will ultimately facilitate reaching the development of new therapeutic approaches. Our main goal is to set-up an intra-sectoral, cross-disciplinary training programme that would prepare the next generation of researchers equipped with advanced theoretical, technical and computational skills to study fundamental aspects of chromatin biology and their impact on CPs. In parallel, Chrom_Rare will devise new strategies to translate the molecular findings into new diagnostic and therapeutic approaches for patients affected by CPs. To enable understanding the molecular basis of chromatinopathies, we aim at developing multiple disease models recapitulating the main clinical features of CPs (WP1), investigating the genetic, epigenetic and topological determinants of CPs (WP2) and uncovering perturbed regulatory circuitries suitable for therapeutic intervention (WP3). Overall Chrom_rare will address unmet socio-economic, medical and scientific needs, for the understanding and possible treatment for CPs.
Palabras clave
Programa(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régimen de financiación
HORIZON-TMA-MSCA-DN - HORIZON TMA MSCA Doctoral NetworksCoordinador
38122 Trento
Italia