写真a

TAKAHASHI Shuntaro

Position

Associate Professor

External Link

Graduating School 【 display / non-display

  • Tokyo Institute of Technology   Faculty of Life Science and Engineering   Graduated

    - 2002.3

Graduate School 【 display / non-display

  • Tokyo Institute of Technology   Graduate School, Division of Life Science and Engineering   Doctor's Course   Completed

    - 2007.3

Studying abroad experiences 【 display / non-display

  • 2005.1
    -
    2005.4

    メルボルン大学   客員研究員

Campus Career 【 display / non-display

  • KONAN UNIVERSITY   Frontier of Institute for Biomolecular Engineering Research in Science and Technology Department of Nanobiochemistry   Associate Professor

    2020.4

  • KONAN UNIVERSITY   Frontier of Institute for Biomolecular Engineering Research in Science and Technology Department of Nanobiochemistry   Lecturer

    2012.6 - 2020.3

External Career 【 display / non-display

  • 東京工業大学   大学院生命理工学研究科

    2012.4 - 2012.5

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    Country:Japan

  • 東京工業大学   大学院生命理工学研究科

    2007.10 - 2012.3

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    Country:Japan

  • 東京工業大学

    2007.4 - 2007.9

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    Country:Japan

Professional Memberships 【 display / non-display

 

Papers 【 display / non-display

  • Pressure-temperature control of activity of RNA polymerase ribozyme. International journal

    Shuntaro Takahashi, Naoki Sugimoto

    Biophysical chemistry   292   106914 - 106914   2022.10

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    A representative role of nucleic acids (DNA and RNA) is in the storage of genetic information. In contrast, RNAs act as ribozymes that catalyze various biochemical reactions. The "RNA world" hypothesis suggests that the origin of life was RNA because a ribozyme that shows RNA replication activity has been identified. However, prebiotic conditions in the RNA world remain unknown. In this study, we investigated the effect of high pressure and temperature on RNA replication using an RNA polymerase ribozyme tC9Y. We found that pressure accelerated the RNA replication activity of tC9Y ribozyme at higher temperatures than physiological conditions. Furthermore, molecular crowding by concentrated polyethylene glycol 200 (average molecular weight 200) synergistically enhanced the replication activity at higher pressure and temperature because the negative effect of a volumetric contribution of hydration on the tC9Y ribozyme activity decreased under crowding conditions. As a comparison, proteinaceous RNA polymerase that exists in the modern era did not show accelerated activity under high pressure and temperature. Thus, these results imply that the prebiotic conditions for the RNA world were at high pressure and temperatures under crowding conditions.

    DOI: 10.1016/j.bpc.2022.106914

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  • Volumetric Strategy for Quantitatively Elucidating a Local Hydration Network around a G-Quadruplex. International journal

    Saki Matsumoto, Shuntaro Takahashi, Sudipta Bhowmik, Tatsuya Ohyama, Naoki Sugimoto

    Analytical chemistry   94 ( 20 )   7400 - 7407   2022.5

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    Hydration around nucleic acids, such as DNA and RNA, is an important factor not only for the stability of nucleic acids but also for their interaction with binding molecules. Thus, it is necessary to quantitatively elucidate the hydration properties of nucleic acids around a certain structure. In this study, volumetric changes in G-quadruplex (G4) RNA formation were investigated by systematically changing the number of G-quartet stacks under high pressure. The volumetric contribution at the level of each G4 structural unit revealed that the core G4 helix was significantly more dehydrated than the other parts, including the edges of G-quartets and loops. These findings will help in predicting the binding of G4 ligands on the surface of G4, depending on the chemical structure of the ligand and solution environment. Therefore, the preset volumetric parameter provides information that can predict molecular interactions in G4 formations during molecular crowding in cells.

    DOI: 10.1021/acs.analchem.2c01075

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  • Replication Control of Human Telomere G-Quadruplex DNA by G-Quadruplex Ligands Dependent on Solution Environment

    Shuntaro Takahashi, Sudipta Bhowmik, Shinobu Sato, Shigeori Takenaka, Naoki Sugimoto

    Life   12 ( 4 )   553 - 553   2022.4

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    Publisher:{MDPI} {AG}  

    The human telomere region is known to contain guanine-rich repeats and form a guanine-quadruplex (G4) structure. As telomeres play a role in the regulation of cancer progression, ligands that specifically bind and stabilize G4 have potential therapeutic applications. However, as the human telomere sequence can form G4 with various topologies due to direct interaction by ligands and indirect interaction by the solution environment, it is of great interest to study the topology-dependent control of replication by ligands. In the present study, a DNA replication assay of a template with a human telomere G4 sequence in the presence of various ligands was performed. Cyclic naphthalene diimides (cNDI1 and cNDI2) efficiently increased the replication stall of the template DNA at G4 with an anti-parallel topology. This inhibition was stability-dependent and topology-selective, as the replication of templates with hybrid or parallel G4 structures was not affected by the cNDI and cNDI2. Moreover, the G4 ligand fisetin repressed replication with selectivity for anti-parallel and hybrid G4 structures without stabilization. Finally, the method used, referred to as quantitative study of topology-dependent replication (QSTR), was adopted to evaluate the correlation between the replication kinetics and the stability of G4. Compared to previous results obtained using a modified human telomere sequence, the relationship between the stability of G4 and the effect on the topology-dependent replication varied. Our results suggest that native human telomere G4 is more flexible than the modified sequence for interacting with ligands. These findings indicate that the modification of the human telomeric sequence forces G4 to rigidly form a specific structure of G4, which can restrict the change in topology-dependent replication by some ligands.

    DOI: 10.3390/life12040553

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  • Ruthenium Polypyridyl Complex Bound to a Unimolecular Chair-Form G-Quadruplex International journal

    Kane T. McQuaid, Shuntaro Takahashi, Lena Baumgaertner, David J. Cardin, Neil G. Paterson, James P. Hall, Naoki Sugimoto, Christine J. Cardin

    Journal of the American Chemical Society   144 ( 13 )   5956 - 5964   2022.4

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    Publisher:American Chemical Society ({ACS})  

    The DNA G-quadruplex is known for forming a range of topologies and for the observed lability of the assembly, consistent with its transient formation in live cells. The stabilization of a particular topology by a small molecule is of great importance for therapeutic applications. Here, we show that the ruthenium complex Λ-[Ru(phen)2(qdppz)]2+ displays enantiospecific G-quadruplex binding. It crystallized in 1:1 stoichiometry with a modified human telomeric G-quadruplex sequence, GGGTTAGGGTTAGGGTTTGGG (htel21T18), in an antiparallel chair topology, the first structurally characterized example of ligand binding to this topology. The lambda complex is bound in an intercalation cavity created by a terminal G-quartet and the central narrow lateral loop formed by T10-T11-A12. The two remaining wide lateral loops are linked through a third K+ ion at the other end of the G-quartet stack, which also coordinates three thymine residues. In a comparative ligand-binding study, we showed, using a Klenow fragment assay, that this complex is the strongest observed inhibitor of replication, both using the native human telomeric sequence and the modified sequence used in this work.

    DOI: 10.1021/jacs.2c00178

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  • Dielectricity of a molecularly crowded solution accelerates NTP misincorporation during RNA-dependent RNA polymerization by T7 RNA polymerase. International journal

    Shuntaro Takahashi, Saki Matsumoto, Pallavi Chilka, Saptarshi Ghosh, Hiromichi Okura, Naoki Sugimoto

    Scientific reports   12 ( 1 )   1149 - 1149   2022.1

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    In biological systems, the synthesis of nucleic acids, such as DNA and RNA, is catalyzed by enzymes in various aqueous solutions. However, substrate specificity is derived from the chemical properties of the residues, which implies that perturbations of the solution environment may cause changes in the fidelity of the reaction. Here, we investigated non-promoter-based synthesis of RNA using T7 RNA polymerase (T7 RNAP) directed by an RNA template in the presence of polyethylene glycol (PEG) of various molecular weights, which can affect polymerization fidelity by altering the solution properties. We found that the mismatch extensions of RNA propagated downstream polymerization. Furthermore, PEG promoted the polymerization of non-complementary ribonucleoside triphosphates, mainly due to the decrease in the dielectric constant of the solution. These results indicate that the mismatch extension of RNA-dependent RNA polymerization by T7 RNAP is driven by the stacking interaction of bases of the primer end and the incorporated nucleotide triphosphates (NTP) rather than base pairing between them. Thus, proteinaceous RNA polymerase may display different substrate specificity with changes in dielectricity caused by molecular crowding conditions, which can result in increased genetic diversity without proteinaceous modification.

    DOI: 10.1038/s41598-022-05136-8

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Books and Other Publications 【 display / non-display

  • Quantitative Analysis of Stall of Replicating DNA Polymerase by G-Quadruplex Formation

    Shuntaro Takahashi, Naoki Sugimoto( Role: Joint author)

    Springer  2019.8 

  • 生体分子化学 基礎から応用まで

    杉本直己・編著( Role: Joint editor)

    講談社  2017.1  ( ISBN:978-4-06-156806-8

  • 生体分子化学 : 基礎から応用まで = biomolecular chemistry

    杉本, 直己, 内藤, 昌信, 橋詰, 峰雄, 高橋, 俊太郎, 田中, 直毅, 建石, 寿枝, 遠藤, 玉樹, 津本, 浩平, 長門石, 曉, 松原, 輝彦, 上田, 実, 朝山, 章一郎, 講談社サイエンティフィク

    講談社  2017.1  ( ISBN:9784061568068

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  • 高圧下での核酸の挙動、CSJカレントレビュー17極限環境の生命化学

    高橋俊太郎,杉本直己( Role: Joint author)

    化学同人  2014.11 

  • バイオセンシングのための水晶発振子マイクロバランス法ー原理から応用例まで

    岡畑恵雄,森俊明,古澤宏幸,高橋俊太郎( Role: Joint editor)

    講談社サイエンティフィク  2013.3 

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Review Papers (Misc) 【 display / non-display

  • 核酸構造のトポロジーを基盤とする遺伝子発現の化学的制御 非二重らせんの構造と機能に関する新概念

    高橋俊太郎

    化学と工業   73 ( 8 )   2020.8

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  • 高圧力が生物関連成分に及ぼす影響-1 高圧力がDNAに及ぼす影響 非標準構造と分子クラウディングの視点

    高橋俊太郎, 杉本直己, 杉本直己

    化学と生物   58 ( 8 )   2020.8

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  • 平成の化学キーワード 核酸の多様性を生みだすもう一つの塩基対相互作用 フーグスティーン塩基対

    高橋俊太郎、杉本直己

    化学   74 ( 5 )   24 - 25   2019.5

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    Authorship:Lead author   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:化学同人  

  • 分子夾雑系の生命化学(2)

    高橋俊太郎、杉本直己

    現代化学   575   34 - 38   2019.2

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    Authorship:Lead author   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:東京化学同人  

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Presentations 【 display / non-display

  • Nucleic Acids Chemistry beyond the Watson-Crick Double Helix (78) : Analysis of structural dynamics of c-Myc G-quadruplex DNA using high pressure

    S. Takahashi, T. Ohyama, S.-B. Chen, J.-H. Tan, N. Sugimoto

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    Event date: 2022.3

  • 脱ワトソン・クリックの核酸化学 (77):高圧環境がDNA非二重らせん構造に与える影響

    大山 達也・高橋 俊太郎・建石 寿枝・田中 成典・杉本 直己

    日本化学会第102回春季年会  (オンライン開催) 

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    Event date: 2022.3

  • Nucleic Acids Chemistry beyond the Watson-Crick Double Helix (80) : Validation of the nearest-neighbor model for Watson-Crick RNA duplexes under molecular crowding condition

    S. Ghosh, S. Takahashi, T. Ohyama, T. Endoh, N. Sugimoto

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    Event date: 2022.3

  • Nucleic Acids Chemistry beyond the Watson-Crick Double Helix (79) : Application of the nearest-neighbor model for the stability prediction of intramolecular i-motif DNAs

    P. Chilka, S. Takahashi, N. Sugimoto

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    Event date: 2022.3

  • Hydration parameters in nearest-neighbor model enables stability prediction for compositionally biased DNA duplexes in molecular crowding conditions

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    Event date: 2021.11

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Industrial property rights 【 display / non-display

  • 核酸合成法

    杉本 直己, 高橋 俊太郎, 大倉 裕道

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    Application no:特願2017-120802

    Announcement no:特開2019-004708

    J-GLOBAL

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Academic Awards Received 【 display / non-display

  • 第29回山下太郎学術研究奨励賞

    2018.6   財団法人 山下太郎顕彰育英会  

    高橋俊太郎

  • 第5回バイオ関連シンポジウム講演賞

    2011.9   日本化学会生体機能関連部会  

    高橋俊太郎

  • The 16th Annual Meeting of the RNA Society Nature Reviews Molecular Cell Biology Poster Prizes(2011)

    2011.6   The RNA Society  

    高橋俊太郎

  • 2010年度 財団法人手島工業教育資金団 手島精一記念研究賞

    2011.2   東京工業大学  

    高橋俊太郎,古澤宏幸,岡畑恵雄

  • 第89回日本化学会年会春期年会 (2009) 優秀講演賞

    2009.3   日本化学会  

    高橋俊太郎

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Grant-in-Aid for Scientific Research 【 display / non-display

  • ミトコンドリア内環境に依存したDNA複製阻害の定量的解析と化学的制御

    2021.4 - 2024.3

    JSPS Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research(C)

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    本研究は、ミトコンドリア内の化学環境変化によってmtDNAの変異が生じる化学的メカニズムを定量的に解明することを目的とする。そのために、本研究ではミトコンドリア内の溶液環境を解析し、その物理化学的な物性を決定する。続いて、決定された溶液物性と同等の物性を有する擬似的なミトコンドリア環境を調整する。その中で四重鎖形成の熱力学的安定性や複製反応の動力学を解析することで、ミトコンドリア内環境での複製阻害効果を定量的に評価する。さらに、溶液の物性を変化させることで、四重鎖構造による複製阻害が生じる化学的環境を系統的に調べ、ミトコンドリア内の化学環境変化に伴うmtDNAの変異発生の関連性を明らかにする。

  • Analysis and regulation of non-canonical nucleic acids under intracellular conditions

    2018.10 - 2021.3

    JSPS Grants-in-Aid for Scientific Research Fund for the Promotion of Joint International Research ( Fostering Joint International Research (B))

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  • 核酸四重鎖のトポロジーで支配される細胞内機能の解明と制御

    2017.4 - 2021.3

    JSPS Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research(C)

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    本研究の目的は、様々なトポロジーを有する核酸四重鎖の熱力学的安定性とDNA複製速度を多角的に定量解析する手法を開発し、核酸四重鎖のトポロジーが持つ生物学的意義を解明することである。開発した解析法を活用することで、四重鎖のトポロジーの違いをターゲットとするという新しいコンセプトに基づく薬剤分子の探索・開発を行い、細胞内機能の人為的制御を目指す。

  • Analysis of Dimensional Code in Central Dogma based on Polymorphic Nucleic Acid Structures

    2016.4 - 2019.3

    JSPS Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research(A)

    Sugimoto Naoki

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    In this study, physicochemical analyses of non-canonical nucleic acid structures were performed in consideration of the effect of chemical environment in cells. The functions of the non-canonical nucleic acid structures, which are assumed as Dimensional Code of central dogma in this research, have been clarified at the molecular level. This study also tried artificial regulation of the Dimensional Code by rationally designing molecules that induce and stabilize the non-canonical nucleic acid structures. Throughout the study, various physicochemical parameters in different chemical environments were obtained. Based on the obtained findings, we designed and synthesized artificial small molecules and nucleic acids that specifically interact with the target non-canonical nucleic acid structure. Furthermore, the molecules were applied for controlling fundamental reactions in central dogma, such as replication, transcription, and translation, both inside and outside cells.

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  • Development of the system to change enzymatic functions without mutational approaches by using molecular crowding

    2016.4 - 2018.3

    JSPS Grants-in-Aid for Scientific Research Grant-in-Aid for challenging Exploratory Research

    SUGIMOTO Naoki

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    We studied the effect of molecular crowding on DNA or RNA polymerization reactions and found that changes in molecular crowding caused the quantity and quality of polymerized products. These phenomenon were the process of gene regulations without protein. Thus, the structure of template nucleic acids played a role for gene expression in the RNA world where there was no protein. Furthermore, we identified that the regulation system is utilized in the modern cells by analysis of living cells. Therefore, in the process of transition from RNA world to DNA world, the gene regulation system by the structure of the template was took over form RNA to DNA.

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Committee Memberships 【 display / non-display

  • 2019   日本高圧力学会  高圧力学会誌編集委員

  • 2010.4 - 2012.3   日本化学会  生体機能関連化学部会若手の会代表幹事

Social Activities 【 display / non-display

  • ひらめき☆ときめきサイエンス 「遺伝子暗号を解く」〜光で操る 遺伝子からタンパク質ができるまで〜

    2013.7

  • ひょうご神戸サイエンスクラスター研究交流会企画委員

    2012.9

  • ひらめき☆ときめきサイエンス 人工DNAによる次世代バイオセンサー –遺伝子の情報を探れ!−

    2012.7