Description du projet
Mieux comprendre la régulation de la transcription dans les pathologies des activateurs génétiques
La transcription est une étape clé de l’expression génétique, où le code transporté par l’ADN est copié sur un brin unique d’ADN, qui sert ensuite de modèle pour constituer la protéine. La régulation de la transcription est la forme la plus courante de contrôle génétique et les activateurs génétiques sont en passe de devenir une cible thérapeutique clé. Les activateurs sont des séquences d’ADN régulatrices qui activent la transcription génétique en se liant à des protéines spécifiques appelées facteurs de transcription. La perturbation de leur fonction est liée à de nombreuses maladies, désormais appelées pathologies des activateurs génétiques, mais leurs mécanismes d’actions restent mal connus. ENHPATHY forme des chercheurs aux techniques pluridisciplinaires nécessaires pour élucider ces mécanismes. L’établissement de partenariats avec des entreprises privées portera les découvertes du laboratoire jusqu’aux patients.
Objectif
Mutations within coding genes have traditionally been considered the major genetic cause of human disease. However, it is becoming increasingly clear that the genetic, structural and/or epigenetic disruption of enhancers and enhancer landscapes represent major etiological factors in numerous human diseases (i.e. enhanceropathies), ranging from rare congenital disorders to common diseases associated with ageing (e.g. cancer, diabetes). Although changes in enhancer activity are predicted to have broad pathological and therapeutic implications, we currently have a limited mechanistic understanding of human enhanceropathies. This reflects, at least partly, our still primitive and partial understanding of the mechanisms whereby enhancers can control gene expression. We hypothesize that enhancers are a diverse group of regulatory sequences that can utilize different mechanisms to control gene expression at the transcriptional and/or post-transcriptional level. Consequently, human enhanceropathies are likely to display an equally diverse molecular basis that, we believe, can only be uncovered using highly multidisciplinary systems biology approaches. Chiefly, elucidating the molecular basis of human enhanceropathies has far reaching translational implications, especially considering the pandemic proportions that some of these disorders are acquiring in recent years. Therefore, the major goal of the ENHPATHY network is to provide early-stage researchers with a multidisciplinary training in which cutting-edge genomic and genetic engineering approaches are ombined with various in vitro and in vivo disease models. Moreover, together with our private partners we aim at translating our molecular findings into new diagnostic and therapeutic strategies.
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MSCA-ITN - Marie Skłodowska-Curie Innovative Training Networks (ITN)Coordinateur
75654 Paris
France