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Understanding parametric translation regulation underlying neuronal functions

Planned Research

Project AreaParametric biology based on translation rate regulatory mechanism
Project/Area Number 20H05786
Research Category

Grant-in-Aid for Transformative Research Areas (B)

Allocation TypeSingle-year Grants
Review Section Transformative Research Areas, Section (III)
Research InstitutionThe University of Tokyo

Principal Investigator

Ikeuchi Yoshiho  東京大学, 生産技術研究所, 准教授 (30740097)

Project Period (FY) 2020-10-02 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥38,090,000 (Direct Cost: ¥29,300,000、Indirect Cost: ¥8,790,000)
Fiscal Year 2022: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
Fiscal Year 2021: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Fiscal Year 2020: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Keywordsオルガノイド / リボソーム / タンパク質合成 / 神経 / 可塑性 / 多電極アレイ / 軸索 / ヒトiPS細胞 / 翻訳 / パラメトリック / 脳 / ALS
Outline of Research at the Start

本研究では柔軟な神経らしさを作り出すパラメトリック翻訳制御の解明を目指す。申請者らがマイクロデバイスを用いてヒトiPS細胞から作製する手法を開発した神経組織を用いることによって、神経活動の強弱に依存する翻訳速度の細胞内局所的変化を網羅的に解析し、神経機能の基盤となる翻訳制御の実態と機構を明らかにする。神経細胞の局所翻訳制御の本質を、領域内で開発される新技術をフル活用することによって生体脳機能へ演繹することにより、柔軟な脳機能を支えるパラメトリックな翻訳制御機構を解明する。

Outline of Final Research Achievements

To understand how the circuit structure of the cerebral connectoid, which connects two cerebral organoids via an axonal bundle, changes neuronal activity, we investigated changes in the internal cellular state focusing on protein synthesis. As a result, we found that the amount of membrane proteins that control axons is increased in connectoids compared to assemblebroids which are two cerebral organoids directly attached to each other. Given that this protein could be the key to controlling the state of the internal network of connectoids, they regulated its activity with agonists and antagonists, and found that it could be used as a method to control the exchange of neural activity between organoids.

Academic Significance and Societal Importance of the Research Achievements

神経回路構造を変化させることで神経活動が変化するが、それに伴って遺伝子発現も変化することを示した。この遺伝子発現が神経活動の制御を行なっており、神経回路の構造、活動、遺伝子発現のそれぞれが密接に絡み合っている様子を試験管内で観察することができた。この知見を実際の脳内の回路に当てはめて検討することによって脳の機能の基盤的機構を調べることができるだろう。また、オルガノイド間の神経活動のやりとりを調節することができたため、同様の手法で脳内の活動を変化させ、領域間の機能的な関連や協調について調べるために役立つと考えられる。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • Research Products

    (18 results)

All 2023 2022 2021 2020

All Journal Article (12 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 12 results,  Open Access: 4 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] High-throughput Assessment of Mitochondrial Protein Synthesis in Mammalian Cells Using Mito-FUNCAT FACS2023

    • Author(s)
      Saito Hironori、Osaki Tatsuya、Ikeuchi Yoshiho、Iwasaki Shintaro
    • Journal Title

      BIO-PROTOCOL

      Volume: 13 Issue: 3

    • DOI

      10.21769/bioprotoc.4602

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human sensory neurons modulate melanocytes through secretion of RGMB2022

    • Author(s)
      Chow Siu Yu A.、Nakayama Kazuki、Osaki Tatsuya、Sugiyama Maki、Yamada Maiko、Takeuchi Hirotaka、Ikeuchi Yoshiho
    • Journal Title

      Cell Reports

      Volume: 40 Issue: 12 Pages: 111366-111366

    • DOI

      10.1016/j.celrep.2022.111366

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Two-photon, red light uncaging of alkyl radicals from organorhodium(III) phthalocyanine complexes2022

    • Author(s)
      Murata Kei、Saibe Yuki、Uchida Mayu、Aono Mizuki、Misawa Ryuji、Ikeuchi Yoshiho、Ishii Kazuyuki
    • Journal Title

      Chemical Communications

      Volume: 58 Issue: 80 Pages: 11280-11283

    • DOI

      10.1039/d2cc03672j

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Advances in construction and modeling of functional neural circuits in vitro2022

    • Author(s)
      Chow Siu Yu A.、Hu Huaruo、Osaki Tatsuya、Levi Timoth?e、Ikeuchi Yoshiho
    • Journal Title

      Neurochemical Research

      Volume: 47 Issue: 9 Pages: 2529-2544

    • DOI

      10.1007/s11064-022-03682-1

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Modeling Axonal Degeneration Using Motor Nerve Organoids2022

    • Author(s)
      Chow Siu Yu A.、Nakanishi Yui、Kaneda Shohei、Ikeuchi Yoshiho
    • Journal Title

      Methods Mol Biol.

      Volume: 2515 Pages: 89-97

    • DOI

      10.1007/978-1-0716-2409-8_6

    • ISBN
      9781071624081, 9781071624098
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Localised light delivery on melanoma cells using optical microneedles2022

    • Author(s)
      Wu Xiaobin、Park Jongho、Chow Siu Yu A.、Kasuya Maria Carmelita Z.、Ikeuchi Yoshiho、Kim Beomjoon
    • Journal Title

      Biomedical Optics Express

      Volume: 13 Issue: 2 Pages: 1045-1045

    • DOI

      10.1364/boe.450456

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Self-Deformable Flexible MEMS Tweezer Composed of Poly(Vinylidene Fluoride)/Ionic Liquid Gel for Electrical Measurements and Soft Gripping2022

    • Author(s)
      Yamaguchi Takafumi、Usami Naoto、Misumi Kei、Toyokura Atsushi、Higo Akio、Ono Shimpei、Hwang Gilgueng、Larrieu Guilhem、Ikeuchi Yoshiho、Tixier-Mita Agnes、Saito Ken、Levi Timothee、Mita Yoshio
    • Journal Title

      Journal of Microelectromechanical Systems

      Volume: 31 Issue: 5 Pages: 802-812

    • DOI

      10.1109/jmems.2022.3187428

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Three-dimensional imaging of the hyperpigmented skin of senile lentigo reveals underlying higher density intracutaneous nerve fibers2021

    • Author(s)
      Nakayama Kazuki、Sassa Shoko、Sugiyama Maki、Kurosumi Motonori、Nishikori Shu、Chow Siu Yu A.、Suzuki Tamio、Ikeuchi Yoshiho
    • Journal Title

      Journal of Dermatological Science

      Volume: - Issue: 1 Pages: 72-75

    • DOI

      10.1016/j.jdermsci.2021.01.010

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability2021

    • Author(s)
      Nagayoshi Y.、Chujo T.、Hirata S.、Nakatsuka H.、Chen C.-W.、Takakura M.、Miyauchi K.、Ikeuchi Y.、Carlyle B. C.、Kitchen R. R.、Suzuki T.、Katsuoka F.、Yamamoto M.、Goto Y.、Tanaka M.、Natsume K.、Nairn A. C.、Suzuki T.、Tomizawa K.、Wei F.-Y.
    • Journal Title

      Science Advances

      Volume: 7 Issue: 13

    • DOI

      10.1126/sciadv.abf3072

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Light-inducible control of cellular proliferation and differentiation by a Hedgehog signaling inhibitor2021

    • Author(s)
      Misawa Ryuji、Minami Tsuyoshi、Okamoto Akimitsu、Ikeuchi Yoshiho
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 38 Pages: 116144-116144

    • DOI

      10.1016/j.bmc.2021.116144

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Three-Dimensional Motor Nerve Organoid Generation2020

    • Author(s)
      Osaki Tatsuya、Chow Siu Yu A.、Nakanishi Yui、Hernandez Joel、Kawada Jiro、Fujii Teruo、Ikeuchi Yoshiho
    • Journal Title

      Journal of Visualized Experiments

      Volume: 163 Issue: 163

    • DOI

      10.3791/61544

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] TFT sensor array for real-time cellular characterization, stimulation, impedance measurement and optical imaging of in-vitro neural cells2020

    • Author(s)
      Shaik Faruk Azam、Ihida Satoshi、Ikeuchi Yoshiho、Tixier-Mita Agnes、Toshiyoshi Hiroshi
    • Journal Title

      Biosensors and Bioelectronics

      Volume: 169 Pages: 112546-112546

    • DOI

      10.1016/j.bios.2020.112546

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] From real-time single to multicompartmental Hodgkin-Huxley neurons on FPGA for bio-hybrid systems.2022

    • Author(s)
      Beaubois R, Khoyratee F, Branchereau P, Ikeuchi Y, Levi T
    • Organizer
      Annu Int Conf IEEE Eng Med Biol Soc.
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Advanced Complexity and Plasticity of Neural Activity in Reciprocally Connected Human Cerebral Organoids2022

    • Author(s)
      Yoshiho Ikeuchi
    • Organizer
      第45回日本神経科学大会/第65回日本神経化学会大会/第32回日本神経回路学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Organoids-on-a-chip models for understanding neuronal circuits and underlying protein synthesis regulations2022

    • Author(s)
      Yoshiho Ikeuchi
    • Organizer
      The 28th Tokyo RNA Club
    • Related Report
      2022 Annual Research Report
  • [Presentation] 末梢神経オルガノイドチップの開発と応用2022

    • Author(s)
      池内与志穂
    • Organizer
      日本末梢神経学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 大脳オルガノイドをつなげて神経回路を創る2022

    • Author(s)
      池内与志穂
    • Organizer
      細胞を創る研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 神経オルガノイドを用いた神経のしなやかな翻訳調節とその機能の探索2022

    • Author(s)
      池内与志穂
    • Organizer
      第95回日本生化学会
    • Related Report
      2022 Annual Research Report

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Published: 2020-10-30   Modified: 2025-01-30  

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