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Elucidation of the mechanism of amyloid fibrillation using Rheo-NMR and development of a new Rheo-NMR instrument

Research Project

Project/Area Number 17K19196
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Biomolecular chemistry and related fields
Research InstitutionKyoto University

Principal Investigator

Sugase Kenji  京都大学, 工学研究科, 准教授 (00300822)

Project Period (FY) 2017-06-30 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
KeywordsRheo-NMR / タンパク質 / アミロイド線維 / NMR / レオロジー / 蛋白質 / 生物物理 / 流体
Outline of Final Research Achievements

Rheo-NMR is a device that allows NMR measurements to be made while shearing a sample in an NMR tube. We have developed a new Rheo-NMR system that can be used with a high-sensitivity cryogenic probe. In this system, a glass rod with an outer diameter of 3 mm is inserted into the NMR tube, and shear flow is generated by rotating only the NMR tube. However, it was very difficult to accurately align the center of the NMR tube and the glass rod with this system. In this study, we have developed a new type of Rheo-NMR system using a jig that can accurately align the glass rod to the center of the NMR tube. With this system, the reproducibility of protein amyloid fibrillation, which was difficult to achieve with the previous system, has been improved.

Academic Significance and Societal Importance of the Research Achievements

高齢化が急速に進む日本では、アルツハイマー病やパーキンソン病などの神経変性疾患が大きな社会問題となっている。神経変性疾患はタンパク質のアミロイド線維化と関連していると言われているが、その機構は良く分かっていない。その理由の1つに、タンパク質のアミロイド線維化過程をリアルタイムかつ原子分解能で解析できるツールがなかったからである。しかし、Rheo-NMRはまさにそのような解析ができる。本研究では、簡便にNMRに設置できる新型のRheo-NMR装置を開発した。アミロイド線維化の再現性も高い。ゆえに、本研究で開発したRheo-NMRは神経変性疾患の新しい治療薬の開発に貢献することなどが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (16 results)

All 2020 2019 2018 2017 Other

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

  • [Int'l Joint Research] Institute of Polymer Research(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Leibniz Institute for Polymer Research(Germany)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Visualizing protein motion in Couette flow by all-atom molecular dynamics2020

    • Author(s)
      Walinda Erik、Morimoto Daichi、Shirakawa Masahiro、Scheler Ulrich、Sugase Kenji
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: 1864 Issue: 2 Pages: 129383-129383

    • DOI

      10.1016/j.bbagen.2019.06.006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 生体分子レオロジーNMRの開発と応用2019

    • Author(s)
      森本 大智、菅瀬 謙治
    • Journal Title

      日本核磁気共鳴学会機関誌

      Volume: 10 Pages: 64-68

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 高感度Rheo-NMRによるアミロイド線維化過程のその場観察2019

    • Author(s)
      森本 大智、菅瀬 謙治
    • Journal Title

      月刊「細胞」

      Volume: 51 Pages: 32-36

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Real-time observation of the interaction between thioflavin T and an amyloid protein by using high-sensitivity Rheo-NMR.2017

    • Author(s)
      Iwakawa N., Morimoto D., Walinda E., Kawata Y., Shirakawa M., Sugase K.
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 18 Issue: 11 Pages: 2271-2271

    • DOI

      10.3390/ijms18112271

    • NAID

      120006501319

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-sensitivity Rheo-NMR spectroscopy for protein studies.2017

    • Author(s)
      Morimoto D., Walinda E., Iwakawa N., Nishizawa M., Kawata Y., Yamamoto A., Shirakawa M., Scheler U., Sugase K.
    • Journal Title

      Anal. Chem.

      Volume: 89 Issue: 14 Pages: 7286-7290

    • DOI

      10.1021/acs.analchem.7b01816

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] In situ Monitoring of Amyloid Fibril Formation Processes Using Rheo-NMR2019

    • Author(s)
      Kenji Sugase, Daichi Morimoto, Walinda Erik, Naoto Iwakawa, Akihiko Yamamoto, Ulrich Scheler
    • Organizer
      8th APNMR
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Amyloid formation of poly-ubiquitin chains investigated by biological rheo-NMR spectroscopy2019

    • Author(s)
      Daichi Morimoto
    • Organizer
      21st EUROMAR
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] High-Sensitivity Rheo-NMR Spectroscopy for Protein Studies2018

    • Author(s)
      Kenji Sugase
    • Organizer
      EUROMAR 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 高感度Rheo-NMRによるタンパク質線維化のその場解析2018

    • Author(s)
      菅瀬謙治
    • Organizer
      日本表面真空学会 2018年9月研究例会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] High-sensitivity Rheo-NMR spectroscopy for protein studies.2017

    • Author(s)
      Sugase K
    • Organizer
      ISMAR 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] High-sensitivity Rheo-NMR spectroscopy for protein studies.2017

    • Author(s)
      Sugase K
    • Organizer
      JGP-Chem Kyoto-Bordeaux Faculty & Student Research Workshop on Chiral Nanostructures for Photonic Applications
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] Research Highlights

    • URL

      http://www.moleng.kyoto-u.ac.jp/~moleng_01/research.html

    • Related Report
      2019 Annual Research Report 2017 Research-status Report
  • [Remarks] Publications

    • URL

      http://www.moleng.kyoto-u.ac.jp/~moleng_01/publications.html

    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 剪断流を発生させる器具2019

    • Inventor(s)
      菅瀬謙治、森本大智、保科好秀
    • Industrial Property Rights Holder
      菅瀬謙治、森本大智、保科好秀
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-111013
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2017-07-21   Modified: 2021-02-19  

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