Investigation of the role of calcium in circadian rhythms

点击翻译按钮获取中文摘要

Virtually all aspects of our physiology and behaviour display 24-hour variations, driven by a circadian clock, which can be found every cell of our body. In mammals, the master clock is present in the brain, which receives light information from the eye and relays it to other tissues in the body to synchronise biological processes with the 24h environmental light-dark cycle. Examples of processes regulated by the clock include the sleep-wake cycle, the regulation of hormone secretion and body temperature and also more complex processes such as cognition and memory formation. Given the importance of clock in regulating large swathes of physiological processes, it's not surprising that disruption of the circadian clock leads to various disorders ranging from diabetes to mood disorders. Whilst there has been great progress in the identification of key proteins involved in the generation of circadian rhythms, we are much further behind in our understanding of how cellular signalling processes influence the circadian clock at the molecular level. Environmental information, such as the time of day are communicated to the molecular clock by signalling mechanisms and an understanding of these mechanisms holds the key to developing drugs that may be used to target the clock.In this application we propose to explore the role of calcium, arguably the most ubiquitous cellular signalling messenger, in regulating circadian rhythms. Calcium signalling plays a major role in regulating how and when genes are turned on and off in response to environmental stimuli in nearly all systems including the heart and brain. Our preliminary work shows that calcium is likely to play a fundamentally important role in the regulatory networks underlying circadian rhythms, and by extension, biological rhythms in all cells. We propose to build upon these findings and conduct a detailed investigation on the role of calcium and the signalling pathways by which it modulates the core molecular clock.