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Chrono-proteinology : Seeking for functional KaiC homologues in mammals

Planned Research

Project AreaChrono-proteinology: principle and design for protein timers
Project/Area Number 21H05132
Research Category

Grant-in-Aid for Transformative Research Areas (B)

Allocation TypeSingle-year Grants
Review Section Transformative Research Areas, Section (III)
Research InstitutionFukui Prefectural University (2023)
Institute for Molecular Science (2021-2022)

Principal Investigator

Mukaiyama Atsushi  福井県立大学, 生物資源学部, 准教授 (80647446)

Co-Investigator(Kenkyū-buntansha) 八木田 和弘  京都府立医科大学, 医学(系)研究科(研究院), 教授 (90324920)
Project Period (FY) 2021-08-23 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
Fiscal Year 2023: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2022: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2021: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords概日時計 / KaiC / 周波数特性 / ATPase / 時計タンパク質 / KaiCホモログ
Outline of Research at the Start

生物は地球の自転による周期的な環境変化に適応するべく、概日時計を用いて生命活動を24時間周期でリズミックに調節している。概日時計のモデル生物であるシアノバクテリアにおいては、唯一種のタンパク質(KaiC)に1回/日の周波数特性がエンコードされており、その特性が多重の階層を貫くように伝播されることで、細胞レベルのリズムの周波数や温度補償性が決定される。本研究では、これまでに蓄積されたKaiCの分子特性に関する知見をもとに、未だ周波数特性がエンコードされた計時因子の実体が掴めていない真核生物における『機能的KaiCホモログ』の探索技術を開発する。

Outline of Final Research Achievements

This research project aims to develop technique to search for clock proteins in mammals that define circadian timescale such as the cyanobacterial clock protein KaiC. We have developed a technique to detect circadian rhythm in a clock reconstructed system using highly sensitive Trp fluorescence probe from KaiC and succeeded in increasing the sensitivity by a factor of 10 or more. We also found that the clock protein complexes were formed at the stage of the emergence of circadian rhythms using an in vitro system that recapitulates the developmental process of mice.

Academic Significance and Societal Importance of the Research Achievements

本成果はKaiCの変異体スクリーニング系の整備により周波数特性を創出する因子(配列機能相関)の同定につながる基盤技術である。今後、マウスの発生過程において概日リズムの出現とともに形成される時計タンパク質複合体についてKaiCの知見と照合することが、哺乳類(マウス)において周波数特性を担う因子の同定につながると期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (25 results)

All 2024 2023 2022 2021

All Journal Article (16 results) (of which Int'l Joint Research: 6 results,  Open Access: 15 results,  Peer Reviewed: 15 results) Presentation (9 results) (of which Invited: 7 results)

  • [Journal Article] Inter-individual variations in circadian misalignment-induced NAFLD pathophysiology in mice2024

    • Author(s)
      Koike Nobuya、Umemura Yasuhiro、Inokawa Hitoshi、Tokuda Isao、Tsuchiya Yoshiki、Sasawaki Yuh、Umemura Atsushi、Masuzawa Naoko、Yabumoto Kazuya、Seya Takashi、Sugimoto Akira、Yoo Seung-Hee、Chen Zheng、Yagita Kazuhiro
    • Journal Title

      iScience

      Volume: 27 Issue: 2 Pages: 108934-108934

    • DOI

      10.1016/j.isci.2024.108934

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of headache response and transcriptomic network by the trigeminal ganglion clock2024

    • Author(s)
      Han Chorong、Lim Ji Ye、Koike Nobuya、Kim Sun Young、Ono Kaori、Tran Celia K.、Mangutov Elizaveta、Kim Eunju、Zhang Yanping、Li Lingyong、Pradhan Amynah A.、Yagita Kazuhiro、Chen Zheng、Yoo Seung‐Hee、Burish Mark J.
    • Journal Title

      Headache: The Journal of Head and Face Pain

      Volume: 64 Issue: 2 Pages: 195-210

    • DOI

      10.1111/head.14670

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Emergence of the circadian clock oscillation during the developmental process in mammals2024

    • Author(s)
      Yagita Kazuhiro
    • Journal Title

      Current Opinion in Genetics & Development

      Volume: 84 Pages: 102152-102152

    • DOI

      10.1016/j.gde.2024.102152

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Master allostery in clock protein KaiC orchestrates circadian rhythm2023

    • Author(s)
      Furuike Yoshihiko , Mukaiyama Atsushi , Akiyama Shuji
    • Journal Title

      SPring-8/SACLA Research Frontiers 2022

      Volume: - Pages: 27-28

    • Related Report
      2023 Annual Research Report
    • Open Access
  • [Journal Article] 概日リズムの基礎, 特集:時間の流れと産婦人科学2023

    • Author(s)
      八木田和弘, 藪本和也
    • Journal Title

      産科と婦人科

      Volume: 90 Pages: 451-458

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of social jetlag and eating patterns with sleep quality and daytime sleepiness in Japanese high school students2023

    • Author(s)
      Yuh Sasawaki, Hitoshi Inokawa, Yukiko Obata, Suzune Nagao, Kazuhiro Yagita
    • Journal Title

      J Sleep Res

      Volume: 32 Issue: 2

    • DOI

      10.1111/jsr.13661

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circadian Features of Cluster Headache and Migraine: A Systematic Review, Meta-analysis, and Genetic Analysis2023

    • Author(s)
      Benkli Barlas、Kim Sun Young、Koike Nobuya、Han Chorong、Tran Celia、Silva Emma、Yan Yuanqing、Yagita Kazuhiro、Chen Zheng、Yoo Seung-Hee、Burish Mark Joseph
    • Journal Title

      Neurology

      Volume: 10 Issue: 22

    • DOI

      10.1212/wnl.0000000000207240

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Highly sensitive tryptophan fluorescence probe for detecting rhythmic conformational changes of KaiC in the cyanobacterial circadian clock system2022

    • Author(s)
      Mukaiyama Atsushi、Furuike Yoshihiko、Yamashita Eiki、Akiyama Shuji
    • Journal Title

      Biochemical Journal

      Volume: 479 Issue: 14 Pages: 1505-1515

    • DOI

      10.1042/bcj20210544

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation mechanisms of the dual ATPase in KaiC2022

    • Author(s)
      Furuike Yoshihiko、Mukaiyama Atsushi、Koda Shin-ichi、Simon Damien、Ouyang Dongyan、Ito-Miwa Kumiko、Saito Shinji、Yamashita Eiki、Nishiwaki-Ohkawa Taeko、Terauchi Kazuki、Kondo Takao、Akiyama Shuji
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 19

    • DOI

      10.1073/pnas.2119627119

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Elucidation of master allostery essential for circadian clock oscillation in cyanobacteria2022

    • Author(s)
      Furuike Yoshihiko、Mukaiyama Atsushi、Ouyang Dongyan、Ito-Miwa Kumiko、Simon Damien、Yamashita Eiki、Kondo Takao、Akiyama Shuji
    • Journal Title

      Science Advances

      Volume: 8 Issue: 15

    • DOI

      10.1126/sciadv.abm8990

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cross-scale analysis of temperature compensation in the cyanobacterial circadian clock system2022

    • Author(s)
      Furuike Yoshihiko、Ouyang Dongyan、Tominaga Taiki、Matsuo Tatsuhito、Mukaiyama Atsushi、Kawakita Yukinobu、Fujiwara Satoru、Akiyama Shuji
    • Journal Title

      Communications Physics

      Volume: 5 Issue: 1 Pages: 75-75

    • DOI

      10.1038/s42005-022-00852-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive Analysis Identified the Circadian Clock and Global Circadian Gene Expression in Human Corneal Endothelial Cells2022

    • Author(s)
      Hiroko Nakai, Yoshiki Tsuchiya, Nobuya Koike, Taiki Asano, Morio Ueno, Yasuhiro Umemura, Yuh Sasawaki, Ryotaro Ono, Jyunji Hamuro, Chie Sotozono, Kazyhiro Yagita
    • Journal Title

      Investigative Ophthalmology & Visual Science

      Volume: 63 Issue: 5 Pages: 1-11

    • DOI

      10.1167/iovs.63.5.16

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adenylate kinase 1 overexpression increases locomotor activity in medaka fish2022

    • Author(s)
      Maruyama Michiyo、Furukawa Yuko、Kinoshita Masato、Mukaiyama Atsushi、Akiyama Shuji、Yoshimura Takashi
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 1 Pages: e0257967-e0257967

    • DOI

      10.1371/journal.pone.0257967

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Slow and temperature-compensated autonomous disassembly of KaiB–KaiC complex2022

    • Author(s)
      Simon Damien、Mukaiyama Atsushi、Furuike Yoshihiko、Akiyama Shuji
    • Journal Title

      Biophysics and Physicobiology

      Volume: 19 Issue: 0 Pages: n/a

    • DOI

      10.2142/biophysico.bppb-v19.0008

    • ISSN
      2189-4779
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The clock modulator Nobiletin mitigates astrogliosis-associated neuroinflammation and disease hallmarks in an Altzheimer's disease model.2022

    • Author(s)
      4.Wiroanto M, Wang C-Y, Kim E, Koike N, Gomez-Gutierrez R, Nohara K, Escobedo Jr G, Choi JM, Han C, Yagita K, Jung SY, Soto C, Lee HK, Morales R, Yoo S-H, Chen Z.
    • Journal Title

      FASEB J.

      Volume: 36 Issue: 3

    • DOI

      10.1096/fj.202101633r

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Circadian key component CLOCK/BMAL1 interferes with segmentation clock in mouse embryonic organoids2021

    • Author(s)
      Umemura Yasuhiro、Koike Nobuya、Tsuchiya Yoshiki、Watanabe Hitomi、Kondoh Gen、Kageyama Ryoichiro、Yagita Kazuhiro
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 1

    • DOI

      10.1073/pnas.2114083119

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 概日時計の周波数特性を備えた時計タンパク質の分子起源解明2023

    • Author(s)
      向山厚
    • Organizer
      第23回日本蛋白質科学会年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 細胞の概日時計形成プロセスにおける蛋白質動態2023

    • Author(s)
      八木田和弘
    • Organizer
      第23回日本蛋白質科学会年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Circadian misalignment-induced pathophysiology in mouse cohort model2023

    • Author(s)
      Yagita Kazuhiro
    • Organizer
      Asian Forum on Chronobiology
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 周波数特性を備えたシアノバクテリア時計タンパク質の分子機構解明2023

    • Author(s)
      向山厚
    • Organizer
      第12回都医学研シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 概日時計の発生と時計タンパク質動態2023

    • Author(s)
      八木田和弘
    • Organizer
      第12回都医学研シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Exploring ancient origins of the circadian clock system through molecular evolution2022

    • Author(s)
      Atsushi Mukaiyama, Yoshihiko Furuike and Shuji Akiyama
    • Organizer
      第60回日本生物物理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 周波数特性を備えた時計タンパク質の分子起源とその進化2022

    • Author(s)
      向山厚、古池美彦、秋山修志
    • Organizer
      第95回日本生化学会年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 分子進化的アプローチに基づく概日時計の進化的起源の探究2022

    • Author(s)
      向山 厚、古池 美彦、秋山 修志
    • Organizer
      令和3年度日本物理学会中部支部講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Exploring ancient origin of circadian oscillation through KaiC evolution2021

    • Author(s)
      Mukaiyama A, Furuike Y, Akiyama S
    • Organizer
      第59回日本生物物理学会年会
    • Related Report
      2021 Annual Research Report
    • Invited

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Published: 2021-10-22   Modified: 2025-01-30  

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