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Photopharmacological regulation of circadian rhythms with caged clock-modulating compounds for investigation of cell-cell interactions

Research Project

Project/Area Number 20K21269
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 38:Agricultural chemistry and related fields
Research InstitutionNagoya University

Principal Investigator

Hirota Tsuyoshi  名古屋大学, トランスフォーマティブ生命分子研究所, 特任准教授 (50372412)

Project Period (FY) 2020-07-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords概日時計 / ケミカルバイオロジー / ケージド化合物 / 細胞間相互作用
Outline of Research at the Start

申請者は概日リズムの周期を変化させる新規化合物を発見して鍵となる制御機構を明らかにしてきた。多細胞から成る概日時計システムの理解に向けて解明すべき重要課題が、細胞間の相互作用である。本研究では時計調節化合物のケージド誘導体を用い、狙ったタイミングに狙った細胞で概日時計を定量的に操作する新技術を生み出す。これを概日リズムの1細胞イメージングに応用し、細胞間相互作用の時空間的な解析に挑戦する。

Outline of Final Research Achievements

Circadian clocks are hierarchically integrated from molecules to organisms in time and space to generate diurnal rhythms of diverse physiological processes. A key challenge in understanding the multicellular circadian clock system is cell-cell communications. In this study, we developed compounds that modulate the function of clock proteins in response to light and enabled temporal control of circadian rhythms in cell populations. By combining these compounds with single-cell imaging of circadian rhythms, we attempted spatial manipulation toward the analysis of cell-cell communications.

Academic Significance and Societal Importance of the Research Achievements

私たちはケミカルバイオロジーの手法を応用し、概日リズムの周期を変化させる新規化合物を発見して鍵となる制御機構を明らかにしてきた。この時計調節化合物と光薬理学を組み合わせることによって、狙ったタイミングに狙った細胞で概日時計を定量的に操作する新技術の開発につながるであろう。光を用いたタンパク質の活性制御という観点から、概日時計分野を超えて広く細胞間相互作用の研究に応用できると期待される。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (42 results)

All 2024 2023 2022 2021 2020 Other

All Int'l Joint Research (8 results) Journal Article (23 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 16 results,  Open Access: 13 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 7 results) Book (2 results) Remarks (2 results)

  • [Int'l Joint Research] University of Southern California(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] University of Southern California(米国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] University of Padova(イタリア)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] University of Groningen(オランダ)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] University of Southern California(米国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Indian Institute of Technology(インド)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] University of Groningen(オランダ)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of Padova(イタリア)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Introduction2024

    • Author(s)
      Cornelissen Germaine、Otsuka Kuniaki、Hirota Tsuyoshi
    • Journal Title

      Chronobiology and Chronomedicine

      Volume: 1 Pages: 1-11

    • DOI

      10.1039/bk9781839167553-00001

    • ISBN
      9781839162008, 9781839167560, 9781839167553
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Journal Article] Quo Vadis2024

    • Author(s)
      Cornelissen Germaine、Hirota Tsuyoshi
    • Journal Title

      Chronobiology and Chronomedicine

      Volume: 1 Pages: 648-664

    • DOI

      10.1039/bk9781839167553-00648

    • ISBN
      9781839162008, 9781839167560, 9781839167553
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Journal Article] Isoform-selective compounds against mammalian circadian clock proteins CRY1 and CRY22023

    • Author(s)
      廣田 毅、羽鳥 恵
    • Journal Title

      生化学

      Volume: 95 Issue: 5 Pages: 604-608

    • DOI

      10.14952/SEIKAGAKU.2023.950604

    • ISSN
      0037-1017
    • Year and Date
      2023-10-25
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a novel PET ligand, [11C]GO289 targeting CK2 expressed in the brain2023

    • Author(s)
      Ogata Aya、Yamada Takashi、Hattori Saori、Ikenuma Hiroshi、Abe Junichiro、Tada Mari、Ichise Masanori、Suzuki Masaaki、Ito Kengo、Kato Takashi、Amaike Kazuma、Hirota Tsuyoshi、Kakita Akiyoshi、Itami Kenichiro、Kimura Yasuyuki
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 90 Pages: 129327-129327

    • DOI

      10.1016/j.bmcl.2023.129327

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of mammalian Cryptochrome with small molecule compounds from in vitro to in vivo2023

    • Author(s)
      Hirota Tsuyoshi
    • Journal Title

      Circadian Clocks

      Volume: 1 Pages: 265-281

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Analysis of the phosphoproteome of CK2α(-/-)/Δα' C2C12 myoblasts compared to the wild-type cells2023

    • Author(s)
      Borgo Christian、Cesaro Luca、Hirota Tsuyoshi、Kuwata Keiko、D'Amore Claudio、Ruppert Thomas、Blatnik Renata、Salvi Mauro、Pinna Lorenzo A.
    • Journal Title

      Open Biology

      Volume: 13 Issue: 2 Pages: 220220-220220

    • DOI

      10.1098/rsob.220220

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phosphorylation of RNA Polymerase II by CDKC;2 Maintains the Arabidopsis Circadian Clock Period2022

    • Author(s)
      Uehara Takahiro N、Nonoyama Takashi、Taki Kyomi、Kuwata Keiko、Sato Ayato、Fujimoto Kazuhiro J、Hirota Tsuyoshi、Matsuo Hiromi、Maeda Akari E、Ono Azusa、Takahara Tomoaki T、Tsutsui Hiroki、Suzuki Takamasa、Yanai Takeshi、Kay Steve A、Itami Kenichiro、Kinoshita Toshinori、Yamaguchi Junichiro、Nakamichi Norihito
    • Journal Title

      Plant and Cell Physiology

      Volume: 63 Issue: 4 Pages: 450-462

    • DOI

      10.1093/pcp/pcac011

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cell-Based Phenotypic Screens to Discover Circadian Clock-Modulating Compounds2022

    • Author(s)
      Hatori Megumi、Hirota Tsuyoshi
    • Journal Title

      Methods Mol Biol

      Volume: 2482 Pages: 95-104

    • DOI

      10.1007/978-1-0716-2249-0_6

    • ISBN
      9781071622483, 9781071622490
    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] CRY2 isoform selectivity of a circadian clock modulator with antiglioblastoma efficacy2022

    • Author(s)
      Miller Simon、Kesherwani Manish、Chan Priscilla、Nagai Yoshiko、Yagi Moeri、Cope Jamie、Tama Florence、Kay Steve A.、Hirota Tsuyoshi
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 40

    • DOI

      10.1073/pnas.2203936119

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A methylbenzimidazole derivative regulates mammalian circadian rhythms by targeting Cryptochrome proteins2022

    • Author(s)
      Yagi Moeri、Miller Simon、Nagai Yoshiko、Inuki Shinsuke、Sato Ayato、Hirota Tsuyoshi
    • Journal Title

      F1000Research

      Volume: 11 Pages: 1016-1016

    • DOI

      10.12688/f1000research.124658.2

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 概日時計の分子機構をケミカルバイオロジーで紐解く2022

    • Author(s)
      松田 智宏、廣田 毅
    • Journal Title

      化学と生物

      Volume: 60 Pages: 212-214

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structural and Chemical Biology Approaches Reveal Isoform-Selective Mechanisms of Ligand Interactions in Mammalian Cryptochromes2022

    • Author(s)
      Miller Simon、Hirota Tsuyoshi
    • Journal Title

      Frontiers in Physiology

      Volume: 13 Pages: 837280-837280

    • DOI

      10.3389/fphys.2022.837280

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemical biology of the circadian clock and its application to drug discovery2021

    • Author(s)
      廣田 毅、松田 智宏
    • Journal Title

      MEDCHEM NEWS

      Volume: 31 Issue: 2 Pages: 62-67

    • DOI

      10.14894/medchem.31.2_62

    • NAID

      130008033651

    • ISSN
      2432-8618, 2432-8626
    • Year and Date
      2021-05-01
    • Related Report
      2021 Research-status Report
  • [Journal Article] Effects of Cryptochrome-modulating compounds on circadian behavioral rhythms in zebrafish2021

    • Author(s)
      Iida M, Nakane Y, Yoshimura T, Hirota T
    • Journal Title

      The Journal of Biochemistry

      Volume: Sep Issue: 5 Pages: 501-507

    • DOI

      10.1093/jb/mvab096

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reversible modulation of circadian time with chronophotopharmacology2021

    • Author(s)
      Kolarski Dusan、Mir-Vinyals Carla、Sugiyama Akiko、Srivastava Ashutosh、Ono Daisuke、Nagai Yoshiko、Iida Mui、Itami Kenichiro、Tama Florence、Szymanski Wiktor、Hirota Tsuyoshi、Feringa Ben L.
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 3164-3164

    • DOI

      10.1038/s41467-021-23301-x

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural differences in the FAD-binding pockets and lid loops of mammalian CRY1 and CRY2 for isoform-selective regulation2021

    • Author(s)
      Miller Simon、Srivastava Ashutosh、Nagai Yoshiko、Aikawa Yoshiki、Tama Florence、Hirota Tsuyoshi
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 26

    • DOI

      10.1073/pnas.2026191118

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Modulation of circadian clock by crude drug extracts used in Japanese Kampo medicine2021

    • Author(s)
      Zhang M, Kobayashi K, Atsumi H, Katada Y, Nakane Y, Chen J, Nagano R, Kadofusa N, Nishiwaki-Ohkawa T, Kon N, Hirota T, Sato A, Makino T, Yoshimura T
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 21038-21038

    • DOI

      10.1038/s41598-021-00499-w

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 概日時計を標的とした化合物と創薬の最前線2021

    • Author(s)
      飯田 夢惟、廣田 毅
    • Journal Title

      Medical Science Digest

      Volume: 47 Pages: 23-25

    • Related Report
      2021 Research-status Report
  • [Journal Article] Structural insights into isoform-selective regulators of mammalian Cryptochromes2021

    • Author(s)
      Miller Simon、Hirota Tsuyoshi
    • Journal Title

      SPring-8 /SACLA Research Frontiers 2020

      Volume: - Pages: 22-23

    • Related Report
      2021 Research-status Report
    • Open Access
  • [Journal Article] Reductive stability evaluation of 6-azopurine photoswitches for the regulation of CKIα activity and circadian rhythms2021

    • Author(s)
      Kolarski Dusan、Sugiyama Akiko、Rodat Theo、Schulte Albert、Peifer Christian、Itami Kenichiro、Hirota Tsuyoshi、Feringa Ben L.、Szymanski Wiktor
    • Journal Title

      Organic & Biomolecular Chemistry

      Volume: 19 Issue: 10 Pages: 2312-2321

    • DOI

      10.1039/d1ob00014d

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparing the efficacy and selectivity of Ck2 inhibitors. A phosphoproteomics approach2021

    • Author(s)
      Borgo Christian、Cesaro Luca、Hirota Tsuyoshi、Kuwata Keiko、D’Amore Claudio、Ruppert Thomas、Blatnik Renata、Salvi Mauro、Pinna Lorenzo A.
    • Journal Title

      European Journal of Medicinal Chemistry

      Volume: 214 Pages: 113217-113217

    • DOI

      10.1016/j.ejmech.2021.113217

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Photopharmacological Manipulation of Mammalian CRY1 for Regulation of the Circadian Clock2021

    • Author(s)
      Kolarski Dusan、Miller Simon、Oshima Tsuyoshi、Nagai Yoshiko、Aoki Yugo、Kobauri Piermichele、Srivastava Ashutosh、Sugiyama Akiko、Amaike Kazuma、Sato Ayato、Tama Florence、Szymanski Wiktor、Feringa Ben L.、Itami Kenichiro、Hirota Tsuyoshi
    • Journal Title

      Journal of the American Chemical Society

      Volume: 143 Issue: 4 Pages: 2078-2087

    • DOI

      10.1021/jacs.0c12280

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 化合物を使って体内時計を操る2020

    • Author(s)
      松田 智宏、廣田 毅
    • Journal Title

      化学

      Volume: 75 Pages: 66-67

    • Related Report
      2020 Research-status Report
  • [Presentation] 時計タンパク質CRYの機能制御化合物と構造ダイナミクス2023

    • Author(s)
      廣田 毅
    • Organizer
      1.日本睡眠学会第45回定期学術集会・第30回日本時間生物学会学術大会合同大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Regulation of mammalian Cryptochrome with small molecule compounds from in vitro to in vivo2022

    • Author(s)
      Hirota Tsuyoshi
    • Organizer
      Sapporo Symposium on Biological Rhythm 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Isoform-selective compounds for mammalian CRY proteins2021

    • Author(s)
      Tsuyoshi Hirota
    • Organizer
      5th Asian Forum on Chronobiology
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 低分子化合物を用いた概日時計タンパク質の機能制御の最先端2021

    • Author(s)
      廣田 毅
    • Organizer
      日本睡眠学会第46回定期学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 哺乳類の階層時計システムの理解に向けた時計タンパク質の調節化合物の開発2021

    • Author(s)
      廣田 毅
    • Organizer
      第28回日本時間生物学会学術大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Chemical biology of the circadian clock and its potential to improve health2021

    • Author(s)
      Tsuyoshi Hirota
    • Organizer
      The 94th Japanese Biochemical Society Meeting
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 時計タンパク質に作用する低分子化合物の開発2020

    • Author(s)
      廣田 毅
    • Organizer
      第41回日本臨床薬理学会学術総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Book] Chronobiology and Chronomedicine2024

    • Author(s)
      Cornelissen, G. and Hirota, T.
    • Total Pages
      716
    • Publisher
      Royal Society of Chemistry
    • ISBN
      9781839162008
    • Related Report
      2023 Annual Research Report
  • [Book] Circadian Clocks2022

    • Author(s)
      Hirota, T., Hatori, M., and Panda, S
    • Total Pages
      429
    • Publisher
      Springer Nature
    • ISBN
      9781071625767
    • Related Report
      2022 Research-status Report
  • [Remarks] 名古屋大学トランスフォーマティブ生命分子研究所Kay-廣田グループ

    • URL

      https://www.itbm.nagoya-u.ac.jp/ja/kay-hirota_group/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 名古屋大学トランスフォーマティブ生命分子研究所Kay-廣田グループ

    • URL

      http://www.itbm.nagoya-u.ac.jp/ja/kay-hirota_group/

    • Related Report
      2022 Research-status Report 2021 Research-status Report 2020 Research-status Report

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Published: 2020-08-03   Modified: 2025-01-30  

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