SSA: Run, eat, sleep, repeat: Hypothalamic integration of homeostatic and circadian signals

保持规律的体育锻炼、饮食和睡眠被认为是享受健康长寿的关键。这样的时间表可以增强我们的24小时生物钟，确保它与我们的社会和物理环境保持最佳一致。反过来，生物钟调节大脑中控制我们吃多少和睡多少的部分。这些大脑区域也与生物钟沟通，因此我们在白天和晚上的适当时间开始和结束我们的饮食和睡眠周期。对日常行为模式的破坏，比如倒班，对我们的健康是有害的，它削弱了我们的生物钟，改变了我们每天锻炼、吃饭、睡觉的时间，也改变了我们吃、喝、休息的时间。这会导致体重过度增加，心脏和精神健康状况不佳。大脑的下丘脑既包含生物钟，也包含调节我们吃多少和睡多少的中枢。不幸的是，用来在生物钟和下丘脑的其他关键区域之间进行交流的大脑化学物质是未知的。一个很好的候选者是大脑的黑素皮质素系统，在这个项目中，学生将用老鼠来研究激活或抑制下丘脑内的黑素皮质素信号如何影响下丘脑对我们进食、睡眠和锻炼的时间和数量的控制。此外，将探讨改变这种大脑化学物质对模拟倒班工作的反应的影响。预计这种化学信号的一些变化将有助于重新调整轮班工作时间表的变化。这项小鼠研究将通过英国生物银行进行补充，并评估人类大脑中黑素皮质素信号的改变是否对睡眠、身体活动和健康有类似的影响。这可能导致开发有用的药剂来对抗轮班工作对健康的长期影响。

Maintaining regular patterns of physical exercise, meals, and sleep are accepted as key to enjoying a long and healthy life. Such schedules act to strengthen our 24h body clock, ensuring that it is optimally aligned with our social and physical environment. In turn, the body clock regulates parts of the brain that control how much we eat and sleep. These brain areas also communicate with the body clock so that we initiate and terminate our meals and sleep cycles at the right times of the day and night. Disruptions to daily patterns in behavior, such as occurs with shiftwork, are detrimental to our health, weakening our body clock and altering both the time of day at which we exercise, eat, and sleep as well how much we eat, drink, and rest. This results in excessive body weight gain and poor heart and mental health.The brain's hypothalamus contains both the body clock as well as the centres that regulate how much we eat and sleep. Unfortunately, the brain chemical that it is used to communicate between the body clock and these other key areas of the hypothalamus is unknown. A good candidate is the brain's melanocortin system and in this project, the student will use mice and study how activating or inhibiting melanocortin signaling within the hypothalamus affects its control of if, when and how much we eat, sleep, and exercise. Further, the effects of altering this brain chemical on the response to simulated shiftwork will be explored. It is anticipated that some changes with this chemical signal will facilitate re-adjustment to changes in shift-work schedules. This mouse work will be complemented by using the UK biobank and evaluating if alterations in melanocortins signaling in the human brain have similar effects on sleep, physical activity, and well-being. This could result with the development of agents useful to combat the long-term health consequences of shiftwork.