Molecular Mechanism of the Circadian Clock in Hibernating Animals: A Calcium-Based Mechanism of Rhythm Oscillation under Low-Temperature

2022 Fiscal Year Final Research Report

• Project Area: Mammalian hibernation biology ~ survival strategies via hypometabolism and hypothermia
• Project/Area Number: 20H05769
• Research Category: Grant-in-Aid for Transformative Research Areas (B)
• Allocation Type: Single-year Grants
• Review Section: Transformative Research Areas, Section (III)
• Research Institution: Center for Novel Science Initatives, National Institutes of Natural Sciences
• Principal Investigator: Enoki Ryosuke 大学共同利用機関法人自然科学研究機構(新分野創成センター、アストロバイオロジーセンター、生命創成探究, 生命創成探究センター, 准教授 (00528341)
• Co-Investigator(Kenkyū-buntansha): 金 尚宏 名古屋大学, 生命農学研究科(WPI), 特任講師 (80822931)
• Project Period (FY): 2020-10-02 – 2023-03-31
• Keywords: 冬眠/休眠 / 概日時計 / 時計遺伝子 / カルシウム / 低温応答 / イメージング

Outline of Final Research Achievements

In mammalian hibernators, a time dependence of the onset and termination of hibernation has been reported. There might be a timekeeping mechanism in the body that can function at low temperatures, and the most likely candidate is the suprachiasmatic nucleus, the master circadian clock in the brain, but whether the transcriptional rhythm of clock genes continues has long been debated. We previously established long-term imaging of intracellular Ca2+ and transcriptional rhythms in the suprachiasmatic nucleus and found that intracellular circadian Ca2+ rhythms persist even in the suprachiasmatic nucleus, where the key clock gene is lacking. This led to the idea that circadian Ca2+ oscillations might be a timekeeping system with a transcription loop-independent oscillation mechanism. In this project, we attempted to elucidate the dynamics of circadian Ca2+ and transcriptional rhythms in the suprachiasmatic nucleus under low-temperature conditions using optical imaging.

Free Research Field

時間生物学

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、代表者の榎木が確立した長期光イメージング計測のアドバンテージを最大限活用し、低温環境下での視交叉上核の概日Ca2+リズムと転写リズムのダイナミクスを光イメージングにより解明することを試みた。また分担者の金は、培養細胞を用いたケミカルバイオロジーの手法を駆使して、概日時計におけるCa2+シグナリングの役割を追求した。本研究により、低温でのリズム発振メカニズムを解明し、冬眠休眠実行の分子ネットワークの核心に迫る結果を得た。