The circadian clock is a basic biological process that enables organisms to anticipate daily environmental changes by adjusting behaviour, physiology and gene regulation. It impacts health and quality of life in regulating sleep and well-being, in the consequences of shift-work, in medical diagnosis/therapy, and in age-related changes. A critical feature of the clock is its synchronisation to the external day (entrainment). Entrainment is the key to understanding the circadian clock and its control mechanisms. In EUCLOCK, highly competitive European researchers join forces to investigate the circadian clock under entrainment using the most advanced methods of functional genomics and phenomics comparing powerful genetic model organisms (humans, mice, flies, and yeast). Its four major innovations will shape the future of circadian research: 1) To compare genomic and phenomic aspects of the clock, SOPs will be developed for the first time that mimic aspects of the natural day (dawn/dusk, day-lengths, etc). 2) Protocols, devices and algorithms will be developed, enabling for the first time large-scale, non-invasive research on human entrainment in the field.3) Developing the first animal models for shift-work, making animals 'work' and feed out of phase with their natural rhythms.The ensuing "dys-entrainment" will be investigated at all levels, aiming to provide the insights needed to treat the symptoms and consequences of human shift-work.4) Building on genome sequences, new genetic components and interactions will be identified that control the circadian clock and its entrainment. For the first time the experimental advantages of yeast will be extensively used. The tractability of yeast permits integration and reconstruction of elements and interactions gleaned from other systems. Together, these approaches allow systems biology research on circadian timing to be performed and integrated at the level of the genome, the proteome, and the metabolome.
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