Objectif The aim of this project is to understand the dynamics of protein-DNA interactomes underlying circadian oscillators in mammals, and how these shape circadian transcriptional output programs. Specifically our goal is to solve a fundamental issue in circadian biology: the phase specificity problem underlying circadian gene expression. We have taken a challenging and original multi-disciplinary approach in which molecular biology experiments will be tightly interlinked with computational analyses and biophysical modeling. The approach will generate time resolved protein-DNA interactomes in mouse liver for several key circadian repressors at unprecedented resolution. These experiments will be complemented with chromosome conformation capture (3C) experiments to monitor how looping interactions and 3D genome structure rearrange during the circadian cycle, which will inform on how circadian transcription networks use long-range gene regulatory mechanisms. Novel computational algorithms based on biophysical principles will be developed and implemented to optimally analyze interactome and 3C datasets. For the latter, statistical models from polymer physics will be used to reconstruct the chromatin networks and interaction maps from the 3C data. At the detailed level of individual cells, we will investigate transcription bursts, and how those are involved in the control of circadian gene expression. In particular we will exploit high temporal resolution bioluminescence reporters using a biophysical model of transcription coupled with a Hidden Markov Model (HMM). Through our innovative approach, we expect that the data generated and state-of-the-art analyses performed will lead novel insight into the role and mechanics of circadian transcription in controlling circadian outputs in mammals. Champ scientifique natural sciencesmathematicsapplied mathematicsstatistics and probabilitynatural sciencesbiological scienceszoologymammalogynatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesmolecular biology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-SG-LS2 - ERC Starting Grant - Genetics,Genomics,Bioinformatics and Systems Biology Appel à propositions ERC-2010-StG_20091118 Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Contribution de l’UE € 1 499 999,88 Adresse BATIMENT CE 3316 STATION 1 1015 Lausanne Suisse Voir sur la carte Région Schweiz/Suisse/Svizzera Région lémanique Vaud Type d’activité Higher or Secondary Education Establishments Contact administratif Caroline Vandevyver (Ms.) Chercheur principal Felix Naef (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Suisse Contribution de l’UE € 1 499 999,88 Adresse BATIMENT CE 3316 STATION 1 1015 Lausanne Voir sur la carte Région Schweiz/Suisse/Svizzera Région lémanique Vaud Type d’activité Higher or Secondary Education Establishments Contact administratif Caroline Vandevyver (Ms.) Chercheur principal Felix Naef (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
