Objectif Circadian clocks are internal daily time keeping mechanisms that are required for autonomous daily rhythms in physiology and behaviour of both fruit flies and humans. Our previous work has identified a developmental role in fruit flies for the transcription factor CLOCK/CYCLE (CLK/CYC), which represents a phylogenetic and functional orthologue of the key human circadian regulator CLOCK/BMAL1. By conditionally manipulating the developmental expression of the genes for CYC as well as the CLK/CYC inhibitor PERIOD (PER), we found that CLK/CYC acts in the clock neurons during metamorphosis to ensure that the adult neural clock circuit maintains the ability to generate circadian locomotor behaviour in constant darkness. The proposed research aims to elucidate this novel role for CLK/CYC by (1) more precisely identifying its spatiotemporal context, (2) determining the associated molecular and cellular phenotypes in adult clock neurons, and (3) systematically testing a number of candidate genes for their involvement in generating the observed phenotypes. Our experimental strategy takes advantage of a combination of fruit fly genetics, confocal immunofluorescence, and behavioural assays that are all well-established in our research group. Ultimately, elucidation of the signalling pathways connecting developmental CLK/CYC activity to overt circadian behaviour in adult flies will provide a compelling rationale for exploring analogous mechanisms associated with the homologous mammalian CLOCK/BMAL and NPAS2/BMAL complexes. Given the association of the Clock and Bmal genes with circadian control of a broad array of physiological functions including metabolism and sleep and the high degree of structural and functional conservation between the clocks of flies and human this study has strong relevance to human health and well-being. Champ scientifique natural sciencesbiological sciencesgeneticsagricultural sciencesagriculture, forestry, and fisheriesagriculturehorticulturefruit growingmedical and health sciencesbasic medicinephysiology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2013-CIG - Marie-Curie Action: "Career Integration Grants" Appel à propositions FP7-PEOPLE-2013-CIG Voir d’autres projets de cet appel Régime de financement MC-CIG - Support for training and career development of researcher (CIG) Coordinateur UNIVERSITY OF SOUTHAMPTON Contribution de l’UE € 100 000,00 Adresse Highfield SO17 1BJ Southampton Royaume-Uni Voir sur la carte Région South East (England) Hampshire and Isle of Wight Southampton Type d’activité Higher or Secondary Education Establishments Contact administratif Yan Qiao (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée