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Development of Fundamental Technique for 4D Chemical Nucleomics

Research Project

Project/Area Number 18K19402
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 47:Pharmaceutical sciences and related fields
Research InstitutionOsaka University

Principal Investigator

Hori Yuichiro  大阪大学, 工学研究科, 准教授 (00444563)

Project Period (FY) 2018-06-29 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
KeywordsChemical Nucleomics / dCas9 / TALE / PYP / Hybrid probe / ハイブリッドプローブ / ゲノム / DNA結合タンパク質 / ラベル化 / ゲノム配列 / 核酸結合色素 / Zinc finger / 4Dケミカルヌクレオミクス / ゲノム編集技術
Outline of Final Research Achievements

In this study, we developed a technique for fluorescent detection of target DNA sequences with the aim of developing a fundamental tool for 4D nucleome analysis to visualize genome dynamics. For this purpose, we will construct a hybrid probe consisting of a DNA-binding protein used for genome editing and a synthetic nucleic acid-binding dye using our protein labeling technology. This hybrid probe was shown to have the ability to bind to the target telomeric DNA sequence and increase the fluorescence intensity.

Academic Significance and Societal Importance of the Research Achievements

蛍光タンパク質を用いたDNA配列の検出技術は、バックグラウンドシグナルの大きなものであるが、本研究のハイブリッドプローブは、DNAへの結合に伴い蛍光強度が増大するため、より高精度に検出できる。DNAの高精度な検出をもとにした4Dヌクレオソーム解析は、ゲノム動態を精密に明らかにすることでき、遺伝子発現制御や疾病発症のメカニズムの解明に繋がる。この観点から、本研究では、ゲノム動態解明のための基盤ツールの開発に成功しており、生命科学や医学の発展に貢献するといえる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (12 results)

All 2021 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 4 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Near-infrared fluorescent probes: a next-generation tool for protein-labeling applications2021

    • Author(s)
      Reja Shahi Imam、Minoshima Masafumi、Hori Yuichiro、Kikuchi Kazuya
    • Journal Title

      Chemical Science

      Volume: 12 Issue: 10 Pages: 3437-3447

    • DOI

      10.1039/d0sc04792a

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fluorogenic probes for detecting deacylase and demethylase activity towards post-translationally-modified lysine residues2021

    • Author(s)
      Hori Yuichiro、Nishiura Miyako、Tao Tomomi、Baba Reisuke、Bull Steven D.、Kikuchi Kazuya
    • Journal Title

      Chemical Science

      Volume: 12 Issue: 7 Pages: 2498-2503

    • DOI

      10.1039/d0sc06551j

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of photoswitchable fluorescent molecules using arylazopyrazole2020

    • Author(s)
      Torii K, Hori Y, Watabe K, Kikuchi K
    • Journal Title

      Bull Chem Soc Jpn.

      Volume: - Issue: 7 Pages: 821-824

    • DOI

      10.1246/bcsj.20200077

    • NAID

      130007879560

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] タンパク質ラベル化技術を用いたメチル化DNAの蛍光イメージング2020

    • Author(s)
      堀 雄一郎
    • Journal Title

      顕微鏡

      Volume: 55 Pages: 90-93

    • NAID

      130007897867

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of Fluorogenic Probes for Rapid High-Contrast Imaging of Transient Nuclear Localization of Sirtuin 32020

    • Author(s)
      Gao J, Hori Y, Shimomura T, Bordy M, Hasserodt J, Kikuchi K
    • Journal Title

      Chembiochem

      Volume: 21 Issue: 5 Pages: 656-662

    • DOI

      10.1002/cbic.201900568

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Live-Cell Imaging of Protein Degradation Utilizing Designed Protein-Tag Mutant and Fluorescent Probe with Turn-Off Switch2020

    • Author(s)
      Gao J, Hori Y, Takeuchi O, Kikuchi K
    • Journal Title

      Bioconjug Chem

      Volume: 31 Issue: 3 Pages: 577-583

    • DOI

      10.1021/acs.bioconjchem.9b00696

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rapid no-wash labeling of PYP-tag proteins with reactive fluorogenic ligands affords stable fluorescent protein conjugates for long-term cell imaging studies2020

    • Author(s)
      Kumar N, Hori, Y. Nishiura M, Kikuchi K
    • Journal Title

      Chem Sci

      Volume: 11 Issue: 14 Pages: 3694-3701

    • DOI

      10.1039/d0sc00499e

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Engineered Protein-tag for Rapid Live-cell Fluorogenic Visualization of Proteins by Anionic Probes2020

    • Author(s)
      Gao J, Hori Y, Nishiura M, Bordy M, Hasserodt J, Kikuchi K
    • Journal Title

      Chem Lett

      Volume: 49 Issue: 3 Pages: 232-235

    • DOI

      10.1246/cl.190875

    • NAID

      130007805930

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chemical Tools with Fluorescence Switches for Verifying Epigenetic Modifications2019

    • Author(s)
      Hori Y, Kikuchi K
    • Journal Title

      Acc Chem Res

      Volume: 52 Issue: 10 Pages: 2849-2857

    • DOI

      10.1021/acs.accounts.9b00349

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Live‐Cell Imaging of DNA Methylation Based on Synthetic‐Molecule/Protein Hybrid Probe2018

    • Author(s)
      Kumar Naresh、Hori Yuichiro、Kikuchi Kazuya
    • Journal Title

      The Chemical Record

      Volume: 18 Issue: 12 Pages: 1672-1680

    • DOI

      10.1002/tcr.201800039

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] PYPタグの新規リガンド構造の探索とマルチカラータンパク質ラベル化プローブの開発2020

    • Author(s)
      堀 雄一郎、西浦美也子、梅野真帆、菊地和也
    • Organizer
      第14回バイオ関連化学シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] Chemical Probes with Fluorogenic Switch for Imaging Modified Protein and DNA2018

    • Author(s)
      Hori, Y.
    • Organizer
      Institute for Protein Research International Seminar “Frontiers in Peptide Science 2018”
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited

URL: 

Published: 2018-07-25   Modified: 2022-01-27  

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