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Identification of molecular networks regulating sleep by in vitro sleep analysis system

Research Project

Project/Area Number 19K16115
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 43060:System genome science-related
Research InstitutionThe University of Tokyo (2021-2022)
Institute of Physical and Chemical Research (2019-2020)

Principal Investigator

Tone Daisuke  東京大学, 大学院医学系研究科(医学部), 助教 (60806610)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords睡眠 / リン酸化 / CaMKII / HTS / 睡眠覚醒サイクル / 分子ネットワーク
Outline of Research at the Start

睡眠覚醒サイクルは身近な生理現象であるにもかかわらず、これを駆動する分子メカニズムは未だ明らかになっていない。本研究では睡眠覚醒を制御する分子ネットワークを効率的に同定するために、ハイスループットなIn vitro睡眠解析系を構築する。この解析系を利用し、睡眠覚醒の制御に関わる新規因子の網羅的探索を行う。更に、同定した新規睡眠制御因子について遺伝子改変動物を利用して詳細な睡眠解析を行い、睡眠制御への寄与を明らかにする。以上のアプローチにより睡眠覚醒制御の分子ネットワークを一斉にあぶり出すことを目指す。

Outline of Final Research Achievements

In this study, we aimed to construct a high-throughput sleep evaluation system and molecular perturbation systems to identify the molecular mechanisms that control sleep/wake cycle. We succeeded in detecting stable neuronal activity in cultured neurons by monitoring calcium signals, providing the basis for the construction of the high-throughput system. As for the molecular perturbation system, we focused on calcium calmodulin-dependent protein kinase (CaMKII), one of the kinases, and revealed a part of the sleep regulation system by perturbing the activity of this molecule.

Academic Significance and Societal Importance of the Research Achievements

我々の研究で明らかとなったCaMKIIによる睡眠制御について、CaMKIIは睡眠の導入に働くのみでなく、睡眠の維持にも重要な役割を果たすことが示唆された。現代では、多くの人が睡眠に問題を抱え、社会問題の一つとなっている。今回の成果がより安定な眠りを実現する新たな睡眠薬の開発や、疾患や老化に伴う睡眠の不安定化を改善する方法につながることが期待できる。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (6 results)

All 2023 2022 2021 2020 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (3 results) Remarks (1 results)

  • [Journal Article] Distinct phosphorylation states of mammalian CaMKIIβ control the induction and maintenance of sleep2022

    • Author(s)
      Daisuke Tone, Koji L Ode, Qianhui Zhang, Hiroshi Fujishima, Rikuhiro G Yamada, et al.
    • Journal Title

      PLOS Biology

      Volume: 20 Issue: 10 Pages: 3001813-3001813

    • DOI

      10.1371/journal.pbio.3001813

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rapid and easy-to-use ES cell manipulation device with a small groove near culturing wells2020

    • Author(s)
      Funano Shun-ichi、Tone Daisuke、Ukai Hideki、Ueda Hiroki R.、Tanaka Yo
    • Journal Title

      BMC Research Notes

      Volume: 13 Issue: 1 Pages: 453-453

    • DOI

      10.1186/s13104-020-05294-w

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Mammalian sleep regulation by phosphorylation states of CaMKII2023

    • Author(s)
      Daisuke Tone
    • Organizer
      日本薬理学会関東部会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Multistep regulation of mammalian sleep by phosphorylation states of CaMKII2022

    • Author(s)
      Daisuke Tone
    • Organizer
      JPW2022
    • Related Report
      2022 Annual Research Report
  • [Presentation] CaMKIIにおける多段階リン酸化による睡眠覚醒サイクル制御2021

    • Author(s)
      戸根大輔、大出晃士、張千惠、上田泰己
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Research-status Report
  • [Remarks] 睡眠に関わるたんぱく質リン酸化酵素の働きを解明

    • URL

      https://www.jst.go.jp/pr/announce/20221005-2/index.html

    • Related Report
      2022 Annual Research Report

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Published: 2019-04-18   Modified: 2024-01-30  

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