Circadian regulation of physiological functions

项目总结 昼夜节律指的是生物功能的每日24小时振荡，在进化上是一种普遍的 从细菌到人类的保守特征。适当的昼夜节律对人类健康很重要，因为慢性 由于时差或夜班工作而导致的昼夜节律紊乱与多种生理缺陷有关 新陈代谢、先天免疫和睡眠。这些缺陷包括感染、炎症、肥胖、 还有糖尿病。许多疾病也会导致昼夜节律的丧失，包括细菌感染和许多 神经系统疾病，如自闭症和帕金森氏症。尽管昼夜节律有着深远的影响 关于人体健康和生理的调节，目前尚不清楚昼夜节律的丧失是如何导致 这些疾病的发展。也就是说，该领域的一个主要空白是识别特定的昼夜节律-- 在不同疾病的发病机制中起作用的调节途径。 我的实验室使用遗传易驯化的模式生物(果蝇和老鼠)来研究 昼夜节律调节的功能和行为在细菌感染和神经系统的发病机制中起作用 疾病模型。本提案的重点是研究：1)新陈代谢在细菌生存中的作用 2)吞噬细胞先天免疫细胞在脆性骨质疏松症模型相关神经功能缺陷中的作用 X综合征，一种同时导致昼夜节律失调和自闭症的人类疾病；以及3)睡眠在 对氧化应激的防御和引起昼夜节律的帕金森氏病果蝇模型 调节失调和睡眠不足。这些在疾病背景下对昼夜节律调节过程的研究 导致昼夜节律失调将有助于阐明其背后的细胞和分子机制。 疾病和确定新的潜在治疗靶点

PROJECT SUMMARY Circadian regulation refers to daily, 24-hour oscillations in biological functions and is a universal, evolutionarily conserved feature from bacteria to humans. Proper circadian regulation is important for human health, as chronic disruption of circadian regulation due to jetlag or night shift work is associated with multiple defects in metabolism, innate immunity, and sleep. These defects include susceptibility to infection, inflammation, obesity, and diabetes. Many diseases also cause loss of circadian regulation, including bacterial infection and many neurological diseases, such as autism and Parkinson’s disease. Despite the profound effects of circadian regulation on human health and physiology, it remains unclear how loss of circadian regulation contributes to the progression of these diseases. That is, a major gap in the field is the identification of specific circadian- regulated pathways that contribute to the pathogenesis of different diseases. My lab uses genetically tractable model organisms (fruit flies and mice) to investigate how disruption of circadian-regulated functions and behaviors contribute to the pathogenesis of bacterial infection and neurological disease models. This proposal focuses on investigating: 1) the role of metabolism in survival of bacterial infection; 2) the role of phagocytic innate immune cells in neurological defects associated with models of Fragile X syndrome, a human disease that causes both circadian dysregulation and autism; and 3) the role of sleep in defense against oxidative stress and the Drosophila model of Parkinson’s disease, which causes circadian dysregulation and sleep loss. These studies of circadian-regulated processes in the context of diseases that lead to circadian dysregulation will help to elucidate the cellular and molecular mechanisms underlying these diseases and identify new potential therapeutic targets