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Financement de l’UE (1 993 059 €) : Le dosage de l’expression génique en tant que moteur des traits cellulaires et physiologiques Hor01/07/2022 Programme de recherche et d'innovation de l'UE « Horizon »
Vue d’ensemble
Texte
Le dosage de l’expression génique en tant que moteur des traits cellulaires et physiologiques
The expression dosage of a gene is a fundamental determinant of its downstream function at the cellular and organismal level, and its genetic or environmental perturbations are a driving force of most common and rare disease in humans. However, we have limited understanding of the specific shape of dosage-to function-curves for human genes, what factors and mechanisms drive their variation across genes, phenotypes and cellular contexts, and how this contributes to functional architecture of human traits. This project addresses these questions using large human genetic data sets and cutting-edge experimental approaches. Using blood cell traits as our study system, we will characterize the relationship between gene dosage and cellular and physiological function in in unprecedented scale and depth. This addresses fundamental questions in systems biology and produces insights that can also benefit genomic medicine and drug development. The Work Packages of this study will: 1) Establish the dosage-to-function relationship for hundreds of human genes, associating genetically driven gene dosage to blood cell traits in large human genetic data, and by an innovative CRISPR-based experimental approach that maps gene dosage changes to multiple cellular phenotypes; 2) Elucidate how cellular the dosage-to-cellular-function relationships differ between cellular states, and use single-cell RNA sequencing to analyze how regulatory networks mediate context-specific dosage-to-function effects; 3) Characterize upstream genomic and environmental regulators of gene dosage. This project will build the first comprehensive, generalizable picture of gene dosage-to-function relationships in humans. Our analysis will link these insights to functional architecture of human traits, providing unique generalizable insights into how disruption of gene dosage and regulatory networks underlies human traits at the cellular and physiological level.
| Kungliga Tekniska Hoegskolan | 1 993 059 € |
https://cordis.europa.eu/project/id/101043238
Cette annonce se réfère à une date antérieure et ne reflète pas nécessairement l’état actuel. L’état actuel est présenté à la page suivante : Kungliga Tekniska Högskolan, Stockholm, Suède.
