Talking to the Clock: Understanding How The Molecular Circadian Clock Is Regulated By The Cellular Environment

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All organisms display daily rhythms in physiology and behaviour, such as the sleep-wake cycle, but also including rhythms in blood pressure, body temperature and cognitive ability. These rhythms are driven by a circadian (circa-around, diem-day) clock that is a molecular pacemaker occurring in most cells throughout the body. In order for this clock to serve its purpose, it must be synchronized to external environmental cues, such as the timing of the day-night cycle and availability of food.Our understanding of how this clock is set to the correct time is very basic. I propose to use cellular models of the clock to understand how external factors both within and external to the cellular environment relay information to the molecular clock and how this information is integrated. We are now realising that disrupted circadian rhythms can lead to a wide range of conditions that impact quality of life and healthy ageing, such as diabetes and mental illness and that the circadian clock represents a novel and untapped target for these conditions. My research will provide new avenues by which the clock can be targeted for therapeutic purposes.This work will be undertaken at the Sleep and Circadian Neuroscience Institute at the University of Oxford in collaboration with the Departments of Pharmacology at Oxford, the University of Geneva, F. Hoffman-La Roche, Basel and Axolabs GmBH, Germany.