Obiettivo The main objective of this interdisciplinary research project is to elucidate regulatory mechanisms through which the circadian timing system coordinates temporal physiology. This system has a hierarchical architecture, in that a master clock in the brain s suprachiasmatic nucleus synchronizes subsidiary oscillators in nearly all body cells. The establishment of phase coherence is obviously of utmost importance in the coordination of circadian physiology. While recent studies have identified feeding cycles, hormone rhythms, and body temperature oscillations as timing cues for peripheral clocks, the molecular makeup of the involved signalling mechanisms is largely unknown. Using liver and cultured cells as model systems, we will employ two innovative strategies for the elucidation of relevant signalling pathways. (1) STAR-Prom (Synthetic TAndem Repeat-PROmoter display), a technique developed in our laboratory, will hopefully identify most if not all immediate early transcription factors activated in cultured cells by rhythmic blood-borne and temperature-dependent signals. (2) A transgenic mouse model with conditionally active liver clocks will be explored in the genome-wide identification of coding and non-coding transcripts whose rhythmic accumulation is system-driven. The in vivo significance of the components emerging from these approaches will be assessed via RNA interference. Thus, relevant siRNAs will be injected into the tail vein of mice, and their effect on the phase of circadian liver gene expression will be monitored in freely moving mice by using whole body fluorescence imaging. Physiologically important components will serve as entry points for the identification of upstream and downstream constituents in the corresponding signal transduction cascades. Campo scientifico medical and health sciencesbasic medicinephysiologynatural sciencesbiological sciencesgeneticsRNA Programma(i) 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) Argomento(i) ERC-AG-LS1 - ERC Advanced Grant - Molecular and Structural Biology and Biochemistry Invito a presentare proposte ERC-2009-AdG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-AG - ERC Advanced Grant Istituzione ospitante UNIVERSITE DE GENEVE Contributo UE € 2 360 136,00 Indirizzo RUE DU GENERAL DUFOUR 24 1211 Geneve Svizzera Mostra sulla mappa Regione Schweiz/Suisse/Svizzera Région lémanique Genève Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Alex Waehry (Dr.) Ricercatore principale Ulrich Schibler (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto UNIVERSITE DE GENEVE Svizzera Contributo UE € 2 360 136,00 Indirizzo RUE DU GENERAL DUFOUR 24 1211 Geneve Mostra sulla mappa Regione Schweiz/Suisse/Svizzera Région lémanique Genève Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Alex Waehry (Dr.) Ricercatore principale Ulrich Schibler (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato