Updated on 2025/05/29

写真a

 
KOJIMA Keiichi
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Lecturer
Position
Lecturer
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Degree

  • 博士(理学) ( 2016.3   京都大学 )

Research Interests

  • 生物物理

  • ロドプシン

  • Photobiology

  • 光受容タンパク質

  • 光操作

  • opsin

  • 光生物

  • 視覚

Research Areas

  • Life Science / Pharmaceutical analytical chemistry and physicochemistry

  • Life Science / Biophysics

  • Life Science / Animal physiological chemistry, physiology and behavioral biology

  • Life Science / Functional biochemistry

Education

  • Kyoto University   理学研究科 生物科学専攻 博士後期課程 (理学博士)  

    2013.4 - 2016.3

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    Country: Japan

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  • Kyoto University   理学研究科 生物科学専攻 博士前期課程  

    2011.4 - 2013.3

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  • Kyoto University   理学部  

    2007.4 - 2011.3

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    Country: Japan

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Research History

  • JST さきがけ研究員(兼任)

    2024.10

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  • 岡山大学学術研究院医歯薬学域, 講師

    2024.4

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  • 岡山大学学術研究院医歯薬学域   助教

    2021.4 - 2024.3

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  • 岡山大学医歯薬学総合研究科   助教

    2017.12 - 2021.3

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  • 岡山大学医歯薬学総合研究科   助教(特任)

    2017.4 - 2017.11

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Professional Memberships

Committee Memberships

  •   生物物理学会 2023・2024年度 理事  

    2023   

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  •   Scientific Reports Editorial Board Member  

    2022   

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  •   生物物理学会 分野別専門委員  

    2021   

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  • 日本生物物理学会 中国四国支部   会計  

    2019.1 - 2020.12   

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    Committee type:Academic society

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  • 日本生物物理学会   平成31年分野別専門委員  

    2019   

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    Committee type:Academic society

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Papers

  • A repertoire of visible light-sensitive opsins in the deep-sea hydrothermal vent shrimp Rimicaris hybisae Reviewed

    Yuya Nagata, Norio Miyamoto, Keita Sato, Yosuke Nishimura, Yuki Tanioka, Yuji Yamanaka, Susumu Yoshizawa, Kuto Takahashi, Kohei Obayashi, Hisao Tsukamoto, Ken Takai, Hideyo Ohuchi, Takahiro Yamashita, Yuki Sudo, Keiichi Kojima

    Journal of Biological Chemistry   110291 - 110291   2025.5

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    Authorship:Last author, Corresponding author   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.jbc.2025.110291

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  • Convergent mechanism underlying the acquisition of vertebrate scotopic vision Reviewed

    Keiichi Kojima, Masataka Yanagawa, Yasushi Imamoto, Yumiko Yamano, Akimori Wada, Yoshinori Shichida, Takahiro Yamashita

    Journal of Biological Chemistry   107175 - 107175   2024.3

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    Authorship:Lead author   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.jbc.2024.107175

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  • A blue-shifted anion channelrhodopsin from the Colpodellida alga Vitrella brassicaformis Reviewed

    Keiichi Kojima, Shiho Kawanishi, Yosuke Nishimura, Masumi Hasegawa, Shin Nakao, Yuya Nagata, Susumu Yoshizawa, Yuki Sudo

    Scientific Reports   13 ( 1 )   2023.4

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    Authorship:Lead author, Corresponding author   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Abstract

    Microbial rhodopsins, a family of photoreceptive membrane proteins containing the chromophore retinal, show a variety of light-dependent molecular functions. Channelrhodopsins work as light-gated ion channels and are widely utilized for optogenetics, which is a method for controlling neural activities by light. Since two cation channelrhodopsins were identified from the chlorophyte alga Chlamydomonas reinhardtii, recent advances in genomic research have revealed a wide variety of channelrhodopsins including anion channelrhodopsins (ACRs), describing their highly diversified molecular properties (e.g., spectral sensitivity, kinetics and ion selectivity). Here, we report two channelrhodopsin-like rhodopsins from the Colpodellida alga Vitrella brassicaformis, which are phylogenetically distinct from the known channelrhodopsins. Spectroscopic and electrophysiological analyses indicated that these rhodopsins are green- and blue-sensitive pigments (λmax =  ~ 550 and ~ 440 nm) that exhibit light-dependent ion channeling activities. Detailed electrophysiological analysis revealed that one of them works as a monovalent anion (Cl, Br and NO3) channel and we named it V. brassicaformis anion channelrhodopsin-2, VbACR2. Importantly, the absorption maximum of VbACR2 (~ 440 nm) is blue-shifted among the known ACRs. Thus, we identified the new blue-shifted ACR, which leads to the expansion of the molecular diversity of ACRs.

    DOI: 10.1038/s41598-023-34125-8

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    Other Link: https://www.nature.com/articles/s41598-023-34125-8

  • Detection of Membrane Potential-Dependent Rhodopsin Fluorescence Using Low-Intensity Light Emitting Diode for Long-Term Imaging Reviewed

    Shiho Kawanishi, Keiichi Kojima, Atsushi Shibukawa, Masayuki Sakamoto, Yuki Sudo

    ACS Omega   2023.1

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    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)   Publisher:American Chemical Society (ACS)  

    DOI: 10.1021/acsomega.2c06980

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  • Phototriggered apoptotic cell death (PTA) using the light-driven outward proton pump rhodopsin Archaerhodopsin-3 Reviewed International journal

    Shin Nakao, Keiichi Kojima, Yuki Sudo

    Journal of the American Chemical Society   144 ( 9 )   3771 - 3775   2022.2

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Chemical Society (ACS)  

    Apoptosis is a type of programmed cell death that commonly occurs in multicellular organisms including humans and that is essential to eliminate unnecessary cells to keep organisms healthy. Indeed, inappropriate apoptosis leads to various diseases such as cancer and autoimmune disease. Here, we developed an optical method to regulate apoptotic cell death by controlling the intracellular pH with outward or inward proton pump rhodopsins, Archaerhodopsin-3 (AR3) or Rubricoccus marinas xenorhodopsin (RmXeR), respectively. The alkalization-induced shrinking of human HeLa cells cultured at pH 9.0 was significantly accelerated or decelerated by light-activated AR3 or RmXeR, respectively, implying the contribution of intracellular alkalization to the cell death. The light-activated AR3 induced cell shrinking at a physiologically neutral pH 7.4 and biochemical analysis revealed that the intracellular alkalization caused by AR3 triggered the mitochondrial apoptotic signaling pathway, which resulted in cell death accompanied by morphological changes. Phototriggered apoptosis (PTA) was also observed for other human cell lines, SH-SY5Y and A549 cells, implying its general applicability. We then used the PTA method with the nematode Caenorhabditis elegans as a model for living animals. Irradiation of transgenic worms expressing AR3 in chemosensing amphid sensory neurons significantly decreased their chemotaxis responses, which suggests that AR3 induced the cell death of amphid sensory neurons and the depression of chemotaxis responses. Thus, the PTA method has a high applicability both in vivo and in vitro, which suggests its potential as an optogenetic tool to selectively eliminate target cells with a high spatiotemporal resolution.

    DOI: 10.1021/jacs.1c12608

    PubMed

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MISC

  • Molecular Diversity of Photosensitive Protein Opsins and Their High Potential for Optogenetic Applications Invited Reviewed

    Keiichi Kojima

    Biological and Pharmaceutical Bulletin   47 ( 10 )   1600 - 1609   2024.10

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    Authorship:Corresponding author   Publisher:Pharmaceutical Society of Japan  

    DOI: 10.1248/bpb.b24-00571

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  • Convergent evolution of animal and microbial rhodopsins

    Keiichi Kojima, Yuki Sudo

    RSC Advances   13 ( 8 )   5367 - 5381   2023

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    Authorship:Lead author, Corresponding author   Publisher:Royal Society of Chemistry (RSC)  

    Animal and microbial rhodopsins have common molecular properties (e.g. protein structure, retinal structure, color sensitivity, and photoreaction) while their functions are distinctively different (e.g. GPCRs versus and ion transporters).

    DOI: 10.1039/d2ra07073a

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  • Molecular mechanism underlying color discrimination ability of frogs and geckos in the dark Reviewed

    Keiichi KOJIMA, Masataka YANAGAWA, Takahiro YAMASHITA

    Hikaku seiri seikagaku(Comparative Physiology and Biochemistry)   39 ( 3 )   122 - 131   2022.12

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    Authorship:Lead author   Publisher:The Japanese Society for Comparative Physiology and Biochemistry  

    DOI: 10.3330/hikakuseiriseika.39.122

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  • Expression of microbial rhodopsins in Escherichia coli and their extraction and purification using styrene-maleic acid copolymers

    Keiichi Kojima, Yuki Sudo

    STAR Protocols   3 ( 1 )   101046 - 101046   2022.3

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    Authorship:Lead author   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.xpro.2021.101046

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  • Microbial Rhodopsins as Multi-functional Photoreactive Membrane Proteins for Optogenetics Reviewed

    Shin Nakao, Keiichi Kojima, Yuki Sudo

    Biological and Pharmaceutical Bulletin   44 ( 10 )   1357 - 1363   2021.10

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    Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:Pharmaceutical Society of Japan  

    DOI: 10.1248/bpb.b21-00544

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Presentations

  • Impact and mechanism of phosphate binding to a light-driven anion transporter SyHR

    18th International Conference on Retinal Proteins  2018 

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  • Bottom-up approach for microbial rhodopsin-based optogenetic tools

    第56回日本生物物理学会  2018 

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  • Phosphate ion binding modulates photochemical properties of a light-driven SO42- transporter, SyHR

    第56回日本生物物理学会  2018 

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  • Evolutionary acquisition of low thermal noise of cone pigments for scotopic vision

    第55回日本生物物理学会  2017 

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  • Optimization mechanism of vertebrate visual pigments for scotopic vision

    International Symposium on Biophysics of Rhodopsins  2017 

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Awards

  • 令和7年度 科学技術分野の文部科学大臣表彰 若手科学者賞

    2025  

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  • 日本薬学会 奨励賞

    2024  

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  • 岡山大学若手トップリサーチャー研究奨励賞

    2023  

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  • 日本光生物学協会 奨励賞

    2022  

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  • 日本薬学会 中国四国支部 奨励賞

    2020  

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Research Projects

  • 多様なロドプシンが紡ぐ非神経系生命機能の光操作技術

    Grant number:23K27142  2023.04 - 2027.03

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    小島 慧一

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    Grant amount:\18720000 ( Direct expense: \14400000 、 Indirect expense:\4320000 )

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  • ロドプシンの個性を生かした生命現象の革新的光操作法の開発

    Grant number:21K15054  2021.04 - 2023.03

    日本学術振興会  科学研究費助成事業  若手研究

    小島 慧一

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    Grant amount:\4550000 ( Direct expense: \3500000 、 Indirect expense:\1050000 )

    本研究では、多様なロドプシン分子の新奇的な性質を生かした革新的な光操作技術の開発を行う。すなわち、申請者らが解析してきた/見出したロドプシンの新奇的な性質を活用することで、動物細胞や個体における様々な生命応答を自在に光操作できる技術基盤を創成する。そのため、交付申請書に記載した実験計画に沿って、「分子特性の理解・改変と最適化」と「分子特性の動物細胞・個体への適用」を進めてきた。
    「分子特性の理解・改変と最適化」に関しては、以下の(1)~(3)に成功した。(1)新規リン酸イオン輸送型ロドプシンの生化学的・分光学的解析を行い、イオン輸送モデルを提唱した。(2)深海生物由来のGPCR型ロドプシンの機能発現系を構築し、分子解析を行った。その結果、高いGq活性化能を持つ可視光吸収型分子の同定に成功した。(3)渦鞭毛藻由来のロドプシン(OmR2)の機能発現系を構築し、分光学的・生化学的・電気生理学的解析を行った。その結果、OmR2がプロトンポンプ機能を持つことを示し、そのイオン輸送機構を明らかにした。
    「分子特性の動物細胞・個体への適用」に関しては、外向きプロトンポンプロドプシンであるAR3または内向きプロトンポンプロドプシンであるRmXeRを多様なヒト培養細胞(HeLa, SH-SY5Yなど)に発現させ、細胞内pHを自在に光で制御できる光操作技術を作出した。さらに、この手法を多様なヒト培養細胞および動物個体(線虫)へと適用し、細胞内のアルカリ化を介してアポトーシス(細胞死)を制御できる新規技術を開発した。

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

    Grant number:19K16090  2019.04 - 2021.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    Keiichi Kojima

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

    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.

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  • 高効率・低ノイズな視細胞応答を実現する視物質の分子メカニズム

    Grant number:15J02054  2015.04 - 2017.03

    日本学術振興会  科学研究費助成事業  特別研究員奨励費

    小島 慧一

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    Grant amount:\2630000 ( Direct expense: \2300000 、 Indirect expense:\330000 )

    多くの脊椎動物の網膜には2種類の視細胞、桿体視細胞と錐体視細胞が存在するが、暗所視を担う桿体視細胞は錐体視細胞と比べて極めて高い光感度を示す。そこで本研究では、桿体視細胞に発現する視物質(ロドプシン、一部の錐体視物質)が分子進化の過程でどのようなアミノ酸残基の置換を経て、暗所視に必須な分子特性(低い熱活性化頻度)を獲得したのかを明らかにすることを目指した。
    昨年度までに、ロドプシンは、錐体視物質からの分子進化の過程で、E112とI189を獲得することで、低い熱活性化頻度を獲得したこと、また桿体視細胞に発現するカエル青錐体視物質や夜行性ヤモリ緑錐体視物質では、ロドプシンと同様に低い熱活性化頻度を示すことを確認していた。本年度では、最初に桿体視細胞に発現する夜行性ヤモリUV錐体視物質の熱活性化頻度を測定し、トカゲや昼行性ヤモリUV錐体視物質と比較した。その結果、夜行性ヤモリのUV錐体視物質のみが低い熱活性化頻度を示した。
    次に、カエル青錐体視物質、夜行性ヤモリ緑・UV錐体視物質の低い熱活性化頻度をもたらすアミノ酸残基の特定を行った。様々な動物種の青・緑・UV錐体視物質のアミノ酸配列を比較し、カエル青錐体視物質、夜行性ヤモリ緑錐体視物質、夜行性ヤモリUV錐体視物質、それぞれでのみ保存されているアミノ酸残基に対して変異体解析を行った。その結果、カエル青錐体視物質ではT47、夜行性ヤモリ緑錐体視物質ではT213、夜行性ヤモリUV錐体視物質ではY89とY172が低い熱活性化頻度に貢献していることが明らかとなった。
    また、測定したすべての野生型視物質およびその変異体の活性状態の安定性を測定した。その結果、発色団の熱異性化頻度と活性状態の安定性の間には強い相関があることが分かった。このことから、発色団の熱異性化頻度は、視物質の発色団周辺の構造揺らぎを反映していると考えられた。

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Class subject in charge

  • Introduction to Communication for Pharmaceutical Sciences (2024academic year) 1st semester  - 火3~4

  • Introduction to Communication for Pharmaceutical Sciences (2024academic year) 1st semester  - 火3~4

  • Analytical Sciences and Physical Chemistry (2024academic year) special  - その他

  • Analytical Sciences and Physical Chemistry (2024academic year) special  - その他

  • Basic Physics (2024academic year) 1st semester  - 火1~2,金3~4

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