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Development of a high-speed luminescence assay of aging chemicals based on molecular events in living subjects

Research Project

Project/Area Number 20K21851
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 63:Environmental analyses and evaluation and related fields
Research InstitutionNational Institute of Advanced Industrial Science and Technology

Principal Investigator

KIM SUNG BAE  国立研究開発法人産業技術総合研究所, エネルギー・環境領域, 主任研究員 (60470043)

Co-Investigator(Kenkyū-buntansha) 小林 紀郎  国立研究開発法人理化学研究所, 情報システム本部, ユニットリーダー (20415160)
桝屋 啓志  国立研究開発法人理化学研究所, バイオリソース研究センター, 室長 (40321814)
Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords発光 / イメージング / 化学物質 / バイオアッセイ / セマンティックウェブ / In Silico / 健康リスク / スクリーニング / 生物発光 / 可視化 / 発光プローブ / 環境リスク / 老化要因物質 / 一分子型生物発光プロ ーブ / AI / ランキング
Outline of Research at the Start

近年、一部の化学物質が寿命に影響することが各種動物実験などで明らかになっており、その分子機序には炎症・酸化・脂質代謝系の核内受容体が深く関与していることが示され
た。本研究では、不特定多数の化学物質を対象に老化要因活性を知識推論アルゴリズム(AI)を用いて効果的に絞り込む。その上位ランクの小分子化学物質を対象に、老化に関わる3大分子イベントを可視化する一分子型発光プローブを設計し、その発光色を指標に「老化要因活性」を高速かつ簡便に判定する発光プラットフォームを創生する。

Outline of Final Research Achievements

During the 2-year’s research period, we conducted an in-silico screening of potential risky chemicals from the database of 50,000 chemicals and ranked the potential impacts on human body. The top-ranked chemicals were further examined if the risks are practical using a highspeed bioluminescence screening system. As the results, we accomplished the development of (i) new bioluminescent substrates, (ii) new single-chain bioluminescent probes, for example, for determining aging chemicals, and (iii) multicolor bioluminescent portfolio. The experimental results were reported in form of 11 scientific journals, reviews, patents, and books.

Academic Significance and Societal Importance of the Research Achievements

生涯にわたる化学物質の非意図的な曝露は潜在的な健康リスクである。当研究は、データベース規模の化学物質より老化要因物質などの健康リスクを効果的に評価する手法を提示するものである。今回のIn Silico研究とWet実験系の技術的融合と連携プレイにより、これまで不可能と思われたデータベース規模の化学物質を対象に、健康リスクという物差しで定量評価できた。今後、化学物質のリスク評価分野において技術的ブレイクスルーを引き起こすことを期待している。また本研究結果は、一般市民にも、化学物質選択の際に、「老化要因性」のような健康リスクを判断資料の一つとして提案するものであり、今後の社会変革に資する研究である。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (32 results)

All 2022 2021 2020 Other

All Journal Article (13 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 13 results,  Open Access: 2 results) Presentation (5 results) Book (10 results) Remarks (1 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] One-Channel Microsliding Luminometer for Quantifying Low-Energy Bioluminescent Lights2022

    • Author(s)
      Sung Bae Kim, Ramasamy Paulmurugan
    • Journal Title

      Methods Mol Biol

      Volume: 2525 Pages: 365-375

    • DOI

      10.1007/978-1-0716-2473-9_28

    • ISBN
      9781071624722, 9781071624739
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Visible Light Bioluminescence Imaging Platform for Animal Cell Imaging2022

    • Author(s)
      Nobuo Kitada, Shojiro Maki, Sung Bae Kim
    • Journal Title

      Methods Mol Biol

      Volume: 2524

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Compact Eight-Channel Light-Sensing System for Bioassays2022

    • Author(s)
      Sung Bae Kim, Sharon Seiko Hori, Negar Sadeghipour, Uday Kumar Sukumar, Ramasamy Paulmurugan
    • Journal Title

      Methods Mol Biol

      Volume: 2525 Pages: 377-386

    • DOI

      10.1007/978-1-0716-2473-9_29

    • ISBN
      9781071624722, 9781071624739
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Quantitative imaging of retinoic acid activities in living mammalian cells2022

    • Author(s)
      Sung Bae Kim, Rika Fujii, Ramasamy Paulmurugan
    • Journal Title

      Methods Mol Biol

      Volume: 2525 Pages: 111-122

    • DOI

      10.1007/978-1-0716-2473-9_8

    • ISBN
      9781071624722, 9781071624739
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Molecular Tension Probe for In Vitro Bioassays2022

    • Author(s)
      Sung-Bae Kim, Rika Fujii, Simon Miller, Mikio Tanabe
    • Journal Title

      Methods Mol Biol

      Volume: 2524 Pages: 91-103

    • DOI

      10.1007/978-1-0716-2453-1_7

    • ISBN
      9781071624524, 9781071624531
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bioluminescent Imaging Systems for Assay Developments2021

    • Author(s)
      KIM Sung-Bae、PAULMURUGAN Ramasamy
    • Journal Title

      Analytical Sciences

      Volume: 37 Issue: 2 Pages: 233-247

    • DOI

      10.2116/analsci.20R003

    • NAID

      130007983504

    • ISSN
      0910-6340, 1348-2246
    • Year and Date
      2021-02-10
    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Color-tunable bioluminescence imaging portfolio for cell imaging2021

    • Author(s)
      Tamaki Shota、Kitada Nobuo、Kiyama Masahiro、Fujii Rika、Hirano Takashi、Kim Sung Bae、Maki Shojiro
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 2219-2219

    • DOI

      10.1038/s41598-021-81430-1

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ligand-Activatable BRET9 Probes for Imaging Molecular Events in Living Mammalian Cells2021

    • Author(s)
      Kim Sung-Bae、Fujii Rika、Paulmurugan Ramasamy
    • Journal Title

      Methods Mol Biol

      Volume: 2274 Pages: 261-270

    • DOI

      10.1007/978-1-0716-1258-3_22

    • ISBN
      9781071612576, 9781071612583
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Highly Bright NIR-BRET System for Imaging Molecular Events in Live Cells2021

    • Author(s)
      Nishihara Ryo、Suzuki Koji、Kim Sung-Bae、Paulmurugan Ramasamy
    • Journal Title

      Methods Mol Biol

      Volume: 2274 Pages: 247-259

    • DOI

      10.1007/978-1-0716-1258-3_21

    • ISBN
      9781071612576, 9781071612583
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Luciferase-Specific Coelenterazine Analogues for Optical Cross Talk-Free Bioassays2021

    • Author(s)
      Nishihara Ryo、Abe Masahiro、Suzuki Koji、Kim Sung-Bae
    • Journal Title

      Methods Mol Biol

      Volume: 2274 Pages: 127-138

    • DOI

      10.1007/978-1-0716-1258-3_12

    • ISBN
      9781071612576, 9781071612583
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Azide- and Dye-Conjugated Coelenterazine Analogues for Imaging Mammalian Cells2021

    • Author(s)
      Nishihara Ryo、Hoshino Emi、Kakudate Yoshiki、Suzuki Koji、Kim Sung-Bae
    • Journal Title

      Methods Mol Biol

      Volume: 2274 Pages: 111-126

    • DOI

      10.1007/978-1-0716-1258-3_11

    • ISBN
      9781071612576, 9781071612583
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Near-Infrared Bioluminescence Imaging of Animal Cells with Through-Bond Energy Transfer Cassette2021

    • Author(s)
      Abe Masahiro、Nishihara Ryo、Kim Sung-Bae、Suzuki Koji
    • Journal Title

      Methods Mol Biol

      Volume: 2274 Pages: 103-110

    • DOI

      10.1007/978-1-0716-1258-3_10

    • ISBN
      9781071612576, 9781071612583
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A New Lineage of Artificial Luciferases for Mammalian Cell Imaging2021

    • Author(s)
      Kim Sung-Bae、Fujii Rika
    • Journal Title

      Methods Mol Biol

      Volume: 2274 Pages: 43-51

    • DOI

      10.1007/978-1-0716-1258-3_5

    • ISBN
      9781071612576, 9781071612583
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Presentation] Highly Sensitive Eight-Channel Light Sensing System for Biomedical Applications2020

    • Author(s)
      金 誠培、Sharon Hori、Ramasamy Paulmurugan
    • Organizer
      日本分析化学会、第69回年会
    • Related Report
      2020 Research-status Report
  • [Presentation] In vitro Determiantion of Rapamycin-Triggered FKBP-FRB Interactions Using a Molecular Tension Probe2020

    • Author(s)
      金 誠培、西原 諒、鈴木 孝治
    • Organizer
      日本分析化学会、第69回年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Color-Tunable Bioluminescence Imaging Platform for Cell Imaging2020

    • Author(s)
      金 誠培、北田 昇雄、牧 昌次郎
    • Organizer
      日本分析化学会、第69回年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Luciferase-Specific Coelenterazine Analogues for Optical Contamination-Free Bioassays2020

    • Author(s)
      金 誠培、西原 諒、Daniel Citterio
    • Organizer
      日本分析化学会、第69回年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Fabrication of a New Lineage of Artificial Luciferases from Natural Luciferase Pools2020

    • Author(s)
      金 誠培、西原 諒、 Daniel Citterio、鈴木 孝治
    • Organizer
      日本分析化学会、第69回年会
    • Related Report
      2020 Research-status Report
  • [Book] Bioluminescence: Methods and Protocols, Volume 12022

    • Author(s)
      Sung-Bae Kim (Ed.)
    • Total Pages
      504
    • Publisher
      Humana Press
    • ISBN
      9781071624524
    • Related Report
      2021 Annual Research Report
  • [Book] Bioluminescence: Methods and Protocols, Volume 22022

    • Author(s)
      Sung-Bae Kim (Ed.)
    • Total Pages
      444
    • Publisher
      Humana Press
    • ISBN
      9781071624722
    • Related Report
      2021 Annual Research Report
  • [Book] Live Cell Imaging: Methods and Protocols (Methods in Molecular Biology, 22742021

    • Author(s)
      Sung-Bae Kim (Ed.)
    • Total Pages
      461
    • Publisher
      Humana Press
    • ISBN
      9781071612576
    • Related Report
      2021 Annual Research Report
  • [Book] Live Cell Imaging”2020

    • Author(s)
      Sung-Bae Kim
    • Total Pages
      447
    • Publisher
      Springer US
    • ISBN
      9781071612576
    • Related Report
      2020 Research-status Report
  • [Book] Chapter 5 “A New Lineage of Artificial Luciferases for Mammalian Cell Imaging”2020

    • Author(s)
      Sung-Bae Kim, Rika Fujii
    • Total Pages
      9
    • Publisher
      Springer US
    • ISBN
      9781071612576
    • Related Report
      2020 Research-status Report
  • [Book] Chapter 10 “Near Infrared Bioluminescence Imaging of Animal Cells with Through-Bond Energy Transfer Cassette”2020

    • Author(s)
      Masahiro Abe, Ryo Nishihara, Sung-Bae Kim, Koji Suzuki
    • Total Pages
      7
    • Publisher
      Springer US
    • ISBN
      9781071612576
    • Related Report
      2020 Research-status Report
  • [Book] Chapter 11 “Azide- and Dye-Conjugated Coelenterazine Analogues for Imaging Mammalian Cells”2020

    • Author(s)
      Ryo Nishihara, Emi Hoshino, Yoshiki Kakudate, Koji Suzuki, Sung-Bae Kim
    • Total Pages
      15
    • Publisher
      Springer US
    • ISBN
      9781071612576
    • Related Report
      2020 Research-status Report
  • [Book] Chapter 12 “Luciferase-Specific Coelenterazine Analogues for Optical Cross-talk-Free Bioassays”2020

    • Author(s)
      Ryo Nishihara, Masahiro Abe, Koji Suzuki, Sung-Bae Kim
    • Total Pages
      12
    • Publisher
      Springer US
    • ISBN
      9781071612576
    • Related Report
      2020 Research-status Report
  • [Book] Chapter 21 “Highly bright NIR-BRET system for imaging molecular events in live cells”2020

    • Author(s)
      Ryo Nishihara, Koji Suzuki, Sung-Bae Kim, Ramasamy Paulmurugan
    • Total Pages
      13
    • Publisher
      Springer US
    • ISBN
      9781071612576
    • Related Report
      2020 Research-status Report
  • [Book] Chapter 22 “Ligand-Activatable BRET9 Probes for Imaging Molecular Events in Living Mammalian Cells”2020

    • Author(s)
      Sung-Bae Kim, Rika Fujii, Ramasamy Paulmurugan
    • Total Pages
      9
    • Publisher
      Springer US
    • ISBN
      9781071612576
    • Related Report
      2020 Research-status Report
  • [Remarks] 全可視光領域で発色する虹色発光標識のポートフォリオを開発

    • URL

      https://www.aist.go.jp/aist_j/press_release/pr2021/pr20210126_2/pr20210126_2.html

    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] 新規セレンテラジン誘導体2022

    • Inventor(s)
      金誠培、牧昌次郎、北田昇雄
    • Industrial Property Rights Holder
      産総研と電通大
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 生物発光酵素の長波長発光基質2020

    • Inventor(s)
      金誠培 牧昌次郎 北田昇雄
    • Industrial Property Rights Holder
      国研)産業技術総合研究所と国大)電気通信大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] マルチチャンネル光検出装置2020

    • Inventor(s)
      金誠培
    • Industrial Property Rights Holder
      国立研究開発法人産業技術総合研究所
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report

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Published: 2020-08-03   Modified: 2023-01-30  

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