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Development of optogenetic tools based on the comprehensive and structural analysis of microbial rhodopsins

Research Project

Project/Area Number 19K16090
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 43040:Biophysics-related
Research InstitutionOkayama University

Principal Investigator

Keiichi Kojima  岡山大学, 医歯薬学総合研究科, 助教 (60819267)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsロドプシン / 光操作 / オプトジェネティクス / 光受容タンパク質 / レチナール / 分子改変 / 生物物理 / 生物物理学
Outline of Research at the Start

光受容膜タンパク質・微生物型ロドプシンは、生物の光利用を支える基礎的な分子としてのみならず、動物細胞や個体の働きを光で操作する技術「オプトジェネティクス(光遺伝学)」における応用研究でも注目されている。しかし、オプトジェネティクスツールとして利用されている分子はごく一部であり、神経系以外での光操作の応用例はほとんど見られない。
本研究では、申請者らが見出した新奇微生物型ロドプシンの分子特性の解析と改変(基礎的研究)を通じて、動物細胞や個体における様々な生命現象(細胞内代謝、恒常性、細胞死など)を光操作する新奇ツールの開発を開拓する。

Outline of Final Research Achievements

Microbial rhodopsin is a family of photoreceptive seven-transmembrane proteins. They have been widely discovered in the three biological domains and show various light-dependent functions, such as ion transporters and light-sensors. Recently, microbial rhodopsins are utilized as central tools in optogenetics that can control the biological functions by light in cells and animals. In this research, we analyzed the structural and functional properties of new microbial rhodopsins and modified them by introducing mutations to understand their functional mechanisms. Based on the molecular analysis, we further developed new optogenetics methods to control several kinds of biological functions.

Academic Significance and Societal Importance of the Research Achievements

近年、ロドプシンは、光で生物個体や細胞の機能を制御する技術・オプトジェネティクス(光遺伝学)のツールとして注目されている。本研究では、オプトジェネティクスの技術基盤を拡大すべく、新たなロドプシン分子の同定と人工分子の開発(例:内向きプロトンポンプ、アニオンチャネル)に成功した。さらに、新しいオプトジェネティクス(例:高感度かつ低毒性な神経抑制、細胞運命の制御)の実証にも成功した。本研究で発見・開発した技術基盤により、様々な生命機能の光操作が可能となり、それら生命機能の分子メカニズムの理解が進むと期待できる。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (28 results)

All 2020 2019

All Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 5 results) Presentation (15 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Green-Sensitive, Long-Lived, Step-Functional Anion Channelrhodopsin-2 Variant as a High-Potential Neural Silencing Tool2020

    • Author(s)
      Kojima Keiichi、Miyoshi Natsuki、Shibukawa Atsushi、Chowdhury Srikanta、Tsujimura Masaki、Noji Tomoyasu、Ishikita Hiroshi、Yamanaka Akihiro、Sudo Yuki
    • Journal Title

      The Journal of Physical Chemistry Letters

      Volume: 11 Issue: 15 Pages: 6214-6218

    • DOI

      10.1021/acs.jpclett.0c01406

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Comparative Studies of the Fluorescence Properties of Microbial Rhodopsins: Spontaneous Emission Versus Photointermediate Fluorescence2020

    • Author(s)
      Kojima Keiichi、Kurihara Rika、Sakamoto Masayuki、Takanashi Tsukasa、Kuramochi Hikaru、Zhang Xiao Min、Bito Haruhiko、Tahara Tahei、Sudo Yuki
    • Journal Title

      The Journal of Physical Chemistry B

      Volume: 124 Issue: 34 Pages: 7361-7367

    • DOI

      10.1021/acs.jpcb.0c06560

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Applicability of Styrene-Maleic Acid Copolymer for Two Microbial Rhodopsins, RxR and HsSRI.2020

    • Author(s)
      Tetsuya Ueta, Keiichi Kojima, Tomoya Hino, Mikihiro Shibata, Shingo Nagano, Yuki Sudo*
    • Journal Title

      Biophysical journal

      Volume: 119 Issue: 9 Pages: 1760-1770

    • DOI

      10.1016/j.bpj.2020.09.026

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lokiarchaeota archaeon schizorhodopsin-2 (LaSzR2) is an inward proton pump displaying a characteristic feature of acid-induced spectral blue-shift2020

    • Author(s)
      Kojima Keiichi、Yoshizawa Susumu、Hasegawa Masumi、Nakama Masaki、Kurihara Marie、Kikukawa Takashi、Sudo Yuki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 20857-20857

    • DOI

      10.1038/s41598-020-77936-9

    • NAID

      120006955824

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Unlimited Potential of Microbial Rhodopsins as Optical Tools2020

    • Author(s)
      Kojima K, Shibukawa A, Sudo Y
    • Journal Title

      Biochemistry

      Volume: 59(3) Issue: 3 Pages: 218-229

    • DOI

      10.1021/acs.biochem.9b00768

    • NAID

      120006939595

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vectorial Proton Transport Mechanism of RxR, a Phylogenetically Distinct and Thermally Stable Microbial Rhodopsin2020

    • Author(s)
      Kojima Keiichi、Ueta Tetsuya、Noji Tomoyasu、Saito Keisuke、Kanehara Kanae、Yoshizawa Susumu、Ishikita Hiroshi、Sudo Yuki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41598-019-57122-2

    • NAID

      120006884916

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] How Does a Microbial Rhodopsin RxR Realize Its Exceptionally High Thermostability with the Proton-Pumping Function Being Retained?2020

    • Author(s)
      Hayashi Tomohiko、Yasuda Satoshi、Suzuki Kano、Akiyama Tomoki、Kanehara Kanae、Kojima Keiichi、Tanabe Mikio、Kato Ryuichi、Senda Toshiya、Sudo Yuki、Murata Takeshi、Kinoshita Masahiro
    • Journal Title

      The Journal of Physical Chemistry B

      Volume: 124 Issue: 6 Pages: 990-1000

    • DOI

      10.1021/acs.jpcb.9b10700

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Methodology for Further Thermostabilization of an Intrinsically Thermostable Membrane Protein Using Amino Acid Mutations with Its Original Function Being Retained2020

    • Author(s)
      Yasuda Satoshi、Akiyama Tomoki、Nemoto Sayaka、Hayashi Tomohiko、Ueta Tetsuya、Kojima Keiichi、Tsukamoto Takashi、Nagatoishi Satoru、Tsumoto Kouhei、Sudo Yuki、Kinoshita Masahiro、Murata Takeshi
    • Journal Title

      Journal of Chemical Information and Modeling

      Volume: 60 Issue: 3 Pages: 1709-1716

    • DOI

      10.1021/acs.jcim.0c00063

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Quantitation of the neural silencing activity of anion channelrhodopsins in Caenorhabditis elegans and their applicability for long-term illumination2019

    • Author(s)
      Yamanashi T, Maki M, Kojima K, Shibukawa A, Tsukamoto T, Chowdhury S, Yamanaka A, Takagi S, Sudo Y
    • Journal Title

      Sci. Rep.

      Volume: 9(1) Issue: 1 Pages: 7863-7863

    • DOI

      10.1038/s41598-019-44308-x

    • NAID

      120006733902

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Photochemical Characterization of a New Heliorhodopsin from the Gram-Negative Eubacterium Bellilinea caldifistulae (BcHeR) and Comparison with Heliorhodopsin-48C122019

    • Author(s)
      Shibukawa A, Kojima K, Nakajima Y, Nishimura Y, Yoshizawa S, Sudo Y
    • Journal Title

      Biochemistry

      Volume: 58(26) Issue: 26 Pages: 2934-2943

    • DOI

      10.1021/acs.biochem.9b00257

    • NAID

      120006847070

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] A distinct lineage of giant viruses brings a rhodopsin photosystem to unicellular marine predators2019

    • Author(s)
      Needham David M.、Yoshizawa Susumu、Hosaka Toshiaki et. al.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 116 Issue: 41 Pages: 20574-20583

    • DOI

      10.1073/pnas.1907517116

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Conformational Differences among Metarhodopsin I, Metarhodopsin II, and Opsin Probed by Wide-Angle X-ray Scattering2019

    • Author(s)
      Imamoto Y, Kojima K, Oka T, Maeda R, Shichida Y
    • Journal Title

      J. Phys. Chem. B

      Volume: 123(43) Issue: 43 Pages: 9134-9142

    • DOI

      10.1021/acs.jpcb.9b08311

    • NAID

      120006764461

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 光受容タンパク質・ロドプシンの 生物物理化学研究2020

    • Author(s)
      小島慧一
    • Organizer
      第59回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Analysis of rhodopsins for a rational understanding and controlling of biological functions2020

    • Author(s)
      小島慧一
    • Organizer
      第58回日本生物物理学会年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ロドプシンの特殊性から学ぶ生物の巧みな光利用法2020

    • Author(s)
      小島慧一
    • Organizer
      2020年度 生物物理学会北海道支部会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] An expanded palette of colorful and powerful fluorescence variants of microbial rhodopsins2020

    • Author(s)
      "Keiichi Kojima, Rika Kurihara, Masayuki Sakamoto, Xiaomin Zhang, Haruhiko Bito, Yuki Sudo "
    • Organizer
      The 1st International Symposium on Molecular Engine_Abstract
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 神経抑制型光遺伝学ツール開発:長いチャネル開時間を示すステップファンクション型緑色光感受性アニオンチャネルの創成2020

    • Author(s)
      小島 慧一、三好 菜月、渋川 敦史、チョドリ スリカンタ、渡邉 宙志、石北 央、山中  章弘、須藤 雄気
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Microbial rhodopsins as a model both for photoactive proteins and optogenetics tools2019

    • Author(s)
      Keiichi Kojima, Yuki Sudo
    • Organizer
      2019 AWEST Awaji Island Conference on Electron Spin Science & Technology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Physicochemical properties of the microbial rhodopsin RxR in the membrane-mimicking molecule styrene maleic acid (SMA) copolymer2019

    • Author(s)
      Tetsuya Ueta, Keiichi Kojima, Tomoya Hino, Mikihiro Shibata, Shingo Nagano & Yuki Sudo
    • Organizer
      第11回日本生物物理学会 中四国支部大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Functional roles of basic amino acid residues in a light-driven SO42- transporter SyHR on its anion transport2019

    • Author(s)
      Masaki Nakama, Keiich Kojima, Marie Kurihara, Susumu Yoshizawa & Yuki Sudo
    • Organizer
      第11回日本生物物理学会 中四国支部大会
    • Related Report
      2019 Research-status Report
  • [Presentation] アニオンチャネルロドプシン(ACR)の超高感度光神経抑制活性と低光毒性2019

    • Author(s)
      山梨 太郎、真木 美紗代、 小島 慧一、渋川 敦史、塚本 卓、チョドリ スリカンタ、山中 章弘、高木 新、須藤 雄気
    • Organizer
      第11回日本生物物理学会 中四国支部大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 線虫C.elegansを用いた光駆動型アニオンチャネルによる超高感度かつ低毒性な光神経抑制の実証2019

    • Author(s)
      山梨 太郎、真木 美紗代, 小島 慧一、渋川 敦史、塚本 卓、高木 新、須藤 雄気
    • Organizer
      日本動物学会第90回大阪大会
    • Related Report
      2019 Research-status Report
  • [Presentation] A WIDE DIVERSITY OF FLUORESCENCE COLOR AND BRIGHTNESS IN MICROBIAL RHODOPSINS2019

    • Author(s)
      Keiichi Kojima, Rika Kurihara, Masayuki Sakamoto, Xiaomin Zhang, Haruhiko Bito, Yuki Sudo
    • Organizer
      17th International Congress on Photobiology, 18thCongress of the European Society for Photobiology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Exploration and development of microbial rhodopsin-based optogenetic tools2019

    • Author(s)
      Keiichi Kojima, Yuki Sudo
    • Organizer
      第57回日本生物物理学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Functional roles of basic amino acids on the anion transport in Synechocystis halorhodopsin (SyHR)2019

    • Author(s)
      Masaki Nakama, Keiichi Kojima, Marie Kurihara, Susumu Yoshizawa, Yuki Sudo
    • Organizer
      第57回日本生物物理学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 神経抑制型光遺伝学ツール開発:アミノ酸置換によるアニオンチャネルロドプシン2の吸収波長およびチャネル開時間の改変2019

    • Author(s)
      小島 慧一、三好 菜月、渡邉 宙志、チョドリ スリカンタ、山中 章弘、石北 央、須藤 雄気
    • Organizer
      第58回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 内向きプロトンポンプ型ロドプシンRmXeRによるヒト子宮頸癌由来HeLa細胞の細胞死抑制効果2019

    • Author(s)
      中尾 新、小島 慧一、 須藤 雄気
    • Organizer
      第58回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 光細胞死制御とその用途2020

    • Inventor(s)
      須藤雄気、小島慧一、中尾新
    • Industrial Property Rights Holder
      須藤雄気、小島慧一、中尾新
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-196718
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report

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Published: 2019-04-18   Modified: 2022-01-27  

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