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Exploitation of new optogenetic tools based on characteristic properties of rhodopsins

Research Project

Project/Area Number 21K15054
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

Kojima Keiichi  岡山大学, 医歯薬学域, 助教 (60819267)

Project Period (FY) 2021-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsロドプシン / 光受容タンパク質 / 光操作 / オプトジェネティクス / 光生物学 / 生物物理学
Outline of Research at the Start

光受容膜タンパク質・ロドプシンは、動物細胞や個体の生理応答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注目されている。近年のゲノム科学の発展により、万を超える多様な分子が見出され、新奇的な性質を示す分子が同定されてきた。しかし、ロドプシンの種類/性質に関係なく、神経活動制御へと適用する流れが一般的であり、他の生理応答制御への適用はほとんど見られない。すなわち、多様なロドプシンのポテンシャルを閉ざしているのが現状である。
本研究では、多様なロドプシン分子の新奇的な性質(=個性)を生かした革新的な光操作技術の開発を行う。

Outline of Final Research Achievements

Rhodopsin is a family of photoreceptive seven-transmembrane proteins containing retinal as a chromophore. They show a variety of photochemical properties (e.g., spectral sensitivity and photoreaction) and molecular functions (e.g., G protein coupled receptors, ion pumps and ion channels). Recently, rhodopsins are utilized as fundamental tools in optogenetics that can control the biological phenomena by light in living cells and oraganisms. In this research, we analyzed the photochemical properties and molecular functions of new rhodopsins from metazoan and microorganisms and to understand their functional mechanisms. Furthermore, we applied new and classical rhodopsins into several cell lines and animals to establish new optogenetics tools.

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のツールとして生命科学分野で注目されている。本研究課題では、生物界に存在する多様なロドプシン分子の解析により、新しい分子(例:青色光感受性アニオンチャネル、可視光感受性Gq活性型ロドプシン、高効率性Naポンプ)を見出し、オプトジェネティクスを支える分子基盤の拡張に成功した。さらに、新しいオプトジェネティクス(例:薬物誘導性膜電位変化観察、細胞死の制御)の開発にも成功した。これらの成果により、様々な生命機能を制御できる光操作技術が進歩し、生命科学分野の発展につながると期待できる。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (42 results)

All 2023 2022 2021

All Journal Article (16 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 16 results,  Open Access: 12 results) Presentation (23 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 2 results)

  • [Journal Article] Identification of a Functionally Efficient and Thermally Stable Outward Sodium-Pumping Rhodopsin (<i>Be</i>NaR) from a Thermophilic Bacterium2023

    • Author(s)
      Kurihara Marie、Thiel Vera、Takahashi Hirona、Kojima Keiichi、Ward David M.、Bryant Donald A.、Sakai Makoto、Yoshizawa Susumu、Sudo Yuki
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 71 Issue: 2 Pages: 154-164

    • DOI

      10.1248/cpb.c22-00774

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2023-02-01
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Detection of Membrane Potential-Dependent Rhodopsin Fluorescence Using Low-Intensity Light Emitting Diode for Long-Term Imaging2023

    • Author(s)
      Kawanishi Shiho、Kojima Keiichi、Shibukawa Atsushi、Sakamoto Masayuki、Sudo Yuki
    • Journal Title

      ACS Omega

      Volume: 8 Issue: 5 Pages: 4826-4834

    • DOI

      10.1021/acsomega.2c06980

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Convergent evolution of animal and microbial rhodopsins2023

    • Author(s)
      Kojima Keiichi、Sudo Yuki
    • Journal Title

      RSC Advances

      Volume: 13 Issue: 8 Pages: 5367-5381

    • DOI

      10.1039/d2ra07073a

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of Monomer/Tetramer Equilibrium of Rod Visual Arrestin in the Interaction with Phosphorylated Rhodopsin2023

    • Author(s)
      Imamoto Yasushi、Kojima Keiichi、Maeda Ryo、Shichida Yoshinori、Oka Toshihiko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 5 Pages: 4963-4963

    • DOI

      10.3390/ijms24054963

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A blue-shifted anion channelrhodopsin from the Colpodellida alga Vitrella brassicaformis2023

    • Author(s)
      Kojima Keiichi、Kawanishi Shiho、Nishimura Yosuke、Hasegawa Masumi、Nakao Shin、Nagata Yuya、Yoshizawa Susumu、Sudo Yuki
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 6974-6974

    • DOI

      10.1038/s41598-023-34125-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular mechanism underlying color discrimination ability of frogs and geckos in the dark2022

    • Author(s)
      KOJIMA Keiichi、YANAGAWA Masataka、YAMASHITA Takahiro
    • Journal Title

      Hikaku seiri seikagaku(Comparative Physiology and Biochemistry)

      Volume: 39 Issue: 3 Pages: 122-131

    • DOI

      10.3330/hikakuseiriseika.39.122

    • ISSN
      0916-3786, 1881-9346
    • Year and Date
      2022-12-07
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of microbial rhodopsins in Escherichia coli and their extraction and purification using styrene-maleic acid copolymers2022

    • Author(s)
      Kojima Keiichi、Sudo Yuki
    • Journal Title

      STAR Protocols

      Volume: 3 Issue: 1 Pages: 101046-101046

    • DOI

      10.1016/j.xpro.2021.101046

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of an Outward Proton Pumping Rhodopsin with a New Record in Thermostability by Means of Amino Acid Mutations2022

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

      The Journal of Physical Chemistry B

      Volume: 126 Issue: 5 Pages: 1004-1015

    • DOI

      10.1021/acs.jpcb.1c08684

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phototriggered Apoptotic Cell Death (PTA) Using the Light-Driven Outward Proton Pump Rhodopsin Archaerhodopsin-32022

    • Author(s)
      Nakao Shin、Kojima Keiichi、Sudo Yuki
    • Journal Title

      Journal of the American Chemical Society

      Volume: 144 Issue: 9 Pages: 3771-3775

    • DOI

      10.1021/jacs.1c12608

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biophysical and Biochemical Research of Animal Rhodopsins2021

    • Author(s)
      Kojima K
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 141 Issue: 10 Pages: 1155-1160

    • DOI

      10.1248/yakushi.21-00144

    • NAID

      130008095282

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2021-10-01
    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Microbial Rhodopsins as Multi-functional Photoreactive Membrane Proteins for Optogenetics2021

    • Author(s)
      Nakao Shin、Kojima Keiichi、Sudo Yuki
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 44 Issue: 10 Pages: 1357-1363

    • DOI

      10.1248/bpb.b21-00544

    • NAID

      130008095840

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2021-10-01
    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] An optogenetic assay method for electrogenic transporters using Escherichia coli co‐expressing light‐driven proton pump2021

    • Author(s)
      Hayashi Masahiro、Kojima Keiichi、Sudo Yuki、Yamashita Atsuko
    • Journal Title

      Protein Science

      Volume: 30 Issue: 10 Pages: 2161-2169

    • DOI

      10.1002/pro.4154

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Functional expression of the eukaryotic proton pump rhodopsin OmR2 in Escherichia coli and its photochemical characterization2021

    • Author(s)
      Kikuchi Masuzu、Kojima Keiichi、Nakao Shin、Yoshizawa Susumu、Kawanishi Shiho、Shibukawa Atsushi、Kikukawa Takashi、Sudo Yuki
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 14765-14765

    • DOI

      10.1038/s41598-021-94181-w

    • NAID

      120007147387

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evolutionary adaptation of visual pigments in geckos for their photic environment2021

    • Author(s)
      Kojima Keiichi、Matsutani Yuki、Yanagawa Masataka、Imamoto Yasushi、Yamano Yumiko、Wada Akimori、Shichida Yoshinori、Yamashita Takahiro
    • Journal Title

      Science Advances

      Volume: 7 Issue: 40 Pages: 109935-109935

    • DOI

      10.1126/sciadv.abj1316

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proton transfer pathway in anion channelrhodopsin-12021

    • Author(s)
      Tsujimura Masaki、Kojima Keiichi、Kawanishi Shiho、Sudo Yuki、Ishikita Hiroshi
    • Journal Title

      eLife

      Volume: 10

    • DOI

      10.7554/elife.72264

    • NAID

      120007183236

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exploring the Retinal Binding Cavity of Archaerhodopsin-3 by Replacing the Retinal Chromophore With a Dimethyl Phenylated Derivative2021

    • Author(s)
      Tsuneishi Taichi、Takahashi Masataka、Tsujimura Masaki、Kojima Keiichi、Ishikita Hiroshi、Takeuchi Yasuo、Sudo Yuki
    • Journal Title

      Frontiers in Molecular Biosciences

      Volume: 8 Pages: 794948-794948

    • DOI

      10.3389/fmolb.2021.794948

    • NAID

      120007183231

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 脊椎動物視物質の暗所視適応メカニズム2022

    • Author(s)
      小島慧一
    • Organizer
      第22回日本光生物学協会年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Evolutionary adaptation of visual pigments in geckos for their photic environment2022

    • Author(s)
      Kojima K, Matsutani Y, Yanagawa M, Imamoto Y, Yamano Y, Wada A, Shichida Y, Yamashita T.
    • Organizer
      19th International Conference on Retinal Proteins
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Phototriggered apoptotic cell death (PTA) using the light-driven outward proton pump rhodopsin Archaerhodopsin-32022

    • Author(s)
      Nakao S, Kojima K, Sudo Y.
    • Organizer
      19th International Conference on Retinal Proteins
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 溶液NMR法を用いたプロトンポンプ型ロドプシンTRとカロテノイドの相互作用解析2022

    • Author(s)
      穂谷野知佳, 鈴木里佳, 廣畑雅史, 村田武士, 小島慧一, 須藤雄気, 高橋栄夫
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 深海に棲むオハラエビRimicaris hybisaeが持つオプシン類の分子機能解析2022

    • Author(s)
      長田祐也, 宮本教生, 佐藤恵太, 山中悠嗣, 西村陽介, 吉澤晋, 高井研, 大内淑代, 山下高廣, 須藤雄気, 小島慧一
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 異なる膜環境におけるプロトンポンプ型ロドプシンRxRの熱安定性、構造および光反応サイクルの比較解析2022

    • Author(s)
      菊間千滉, 鈴木里佳, 藤田陽, 廣畑雅史, 小島慧一, 須藤雄気, 高橋栄夫
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 光照射溶液NMR法によるプロトンポンプ型ロドプシン RxRの光反応サイクル後期中間体の局所構造解析2022

    • Author(s)
      廣西麗加, 鈴木里佳, 小島慧一, 須藤雄気, 長島敏雄, 山崎俊夫, 高橋栄夫
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 新奇薬物送達キャリアーとしての内向きプロトンポンプロドプシンRmXeR内包型光誘起崩壊リポソーム(LiDL)の開発2022

    • Author(s)
      恒石泰地, 小島慧一, 窪田文佳, 山田勇磨, 須藤雄気
    • Organizer
      第43回 生体膜と薬物の相互作用シンポジウム
    • Related Report
      2022 Annual Research Report
  • [Presentation] LED光源を用いたアーキロドプシン3(AR3)による長時間膜電位計測法の確立2022

    • Author(s)
      川西志歩, 小島慧一, 渋川敦史, 坂本雅行, 須藤雄気
    • Organizer
      第43回 生体膜と薬物の相互作用シンポジウム
    • Related Report
      2022 Annual Research Report
  • [Presentation] Long-term membrane voltage imaging by microbial rhodopsin AR3 with LED light source2022

    • Author(s)
      Kawanishi S, Kojima K, Shibukawa A, Sakamoto M, Sudo Y.
    • Organizer
      第 60回日本生物物理学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Molecular properties of opsins from the deep-sea hydrothermal vent shrimp Rimicaris hybisae2022

    • Author(s)
      Kojima K, Nagata Y, Miyamoto N, Sato K, Yamanaka Y, Nishimura Y, Yoshizawa S, Takai K, Ohuchi H, Yamashita T, Sudo Y.
    • Organizer
      第 60回日本生物物理学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Development a Method for Phototriggered Apoptotic Cell Death (PTA) Using the LightDriven Proton Pump Protein Archaerhodopsin-32022

    • Author(s)
      中尾新, 小島慧一, 須藤雄気
    • Organizer
      第22回 日本蛋白質科学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Development of light-induced disruptive liposome (LiDL) with a light-driven inward proton pump rhodopsin RmXeR2022

    • Author(s)
      Tsuneishi T, Kojima K, Kubota F, Yamada Y, Sudo Y.
    • Organizer
      第13回 日本生物物理学会中国四国支部大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 新規高効率ナトリウムポンプロドプシンBeNaRの機能・分子特性解析とNa+ポンプモデルの提唱2022

    • Author(s)
      栗原 眞理恵, 吉澤晋, 高橋広奈, 橋本美沙, 小島慧一, 塚本卓, 菊川峰志, 酒井誠, 須藤雄気
    • Organizer
      第13回 日本生物物理学会中国四国支部大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] LED光源を用いたロドプシン蛍光観察システムの構築と膜電位の長時間イメージングへの展開2022

    • Author(s)
      小島慧一, 川西志歩, 渋川敦史, 坂本雅行, 須藤 雄気
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 外向きプロトンポンプ型ロドプシンを用いた光アポトーシス誘導法の開発2022

    • Author(s)
      中尾新, 小島慧一, 須藤雄気
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Research-status Report
  • [Presentation] Archaerhodopsin-3 (AR3) における発色団レチナールのジメチルフェニル誘導体への置換と機 能・光化学的解析2021

    • Author(s)
      恒石泰地, 辻村真樹, 高橋雅崇, 小島慧一, 石北央, 竹内靖雄, 須藤雄気
    • Organizer
      日本生物物理学会 中国四国支部大会(第12回)
    • Related Report
      2021 Research-status Report
  • [Presentation] LED光源を用いたアーキロドプシン 3 由来の膜電位感受性蛍光の観察2021

    • Author(s)
      川西志歩, 小島慧一, 渋川敦史, 坂本雅行, 須藤雄気
    • Organizer
      日本生物物理学会 第12回中国四国支部大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Optical control of apoptotic cell death with light-driven proton pump rhodopsins2021

    • Author(s)
      Nakao S, Kojima K, Sudo Y
    • Organizer
      日本生物物理学会 第12回中国四国支部大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 光駆動性アニオン輸送体(SyHR)が示すリン酸輸送能と大腸菌べん毛運動の光操作への適用2021

    • Author(s)
      中西浩太郎, 小島慧一,曽和義幸,須藤雄気
    • Organizer
      第42回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] Development of light-induced disruptive liposome (LiDL) with an inward proton pump rhodopsin RmXeR2021

    • Author(s)
      Tsuneishi T, Kojima K, Kubota F, Yamada Y, Sudo Y
    • Organizer
      第 59回日本生物物理学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Detection of membrane potential-dependent rhodopsin fluorescence with LED system for longterm imaging2021

    • Author(s)
      Kawanishi S, Kojima K, Shibukawa A, Sakamoto M, Sudo Y
    • Organizer
      第 59回日本生物物理学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Optical control of apoptotic cell death by light-driven proton pumps2021

    • Author(s)
      Kojima K, Nakao S, Sudo Y
    • Organizer
      第 59回日本生物物理学会
    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] 光合成生物の形質転換体およびその用途2022

    • Inventor(s)
      須藤雄気, 小島慧一
    • Industrial Property Rights Holder
      須藤雄気, 小島慧一
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2022 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 光合成生物の形質転換体およびその用途2021

    • Inventor(s)
      須藤雄気, 小島慧一
    • Industrial Property Rights Holder
      須藤雄気, 小島慧一
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-089800
    • Filing Date
      2021
    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] 光により細胞死を制御する方法2021

    • 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
    • Filing Date
      2021
    • Related Report
      2021 Research-status Report
    • Overseas

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Published: 2021-04-28   Modified: 2024-01-30  

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