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Adaptive optics approach for high-throughput, high-resolution cryo-electron microscopy of biological macromolecules and complexes

Research Project

Project/Area Number 19K21176
Project/Area Number (Other) 18H06043 (2018)
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund (2019)
Single-year Grants (2018)
Review Section 0701:Biology at molecular to cellular levels, and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Danev Radostin  東京大学, 大学院医学系研究科(医学部), 教授 (50415931)

Project Period (FY) 2018-08-24 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordscryo-electron microscopy / molecular structure / single particle analysis / data acquisition
Outline of Research at the Start

This research is aimed to greatly improve the productivity and efficiency of data collection with cryo-electron microscopy. Cryo-electron microscopes are expensive instruments, both to purchase and to maintain/support. By increasing the number of images that can be collected each day, we will reduce the overall cost of research projects and improve the efficiency of use of these expensive instruments. The improved data collection speed will also allow more researchers to have access to the microscopes and therefore it will increase the productivity of cryo-electron microscopy facilities.

Outline of Final Research Achievements

Cryo-electron microscopy is a powerful technique that can determine the three-dimensional structure of proteins with high-resolution. It requires the acquisition of thousands of images from the sample. Previously, several days of data collection were required to produce a high-quality result. This was not very efficient because only a few researchers could use the expensive electron microscope every month. In this project, we developed and applied in practice a method that improved the image acquisition speed more than five times. Before, we could collect only about 1000 images per day. Now, we are collecting on average about 5500 images every day. This greatly improved the efficiency of the experiments and allowed more researchers to use the microscope.

Academic Significance and Societal Importance of the Research Achievements

低温電子顕微鏡における画像取得の大幅な速度改善により、タンパク質の構造研究の加速が期待されます。 生体分子の機能を理解するには、構造を知ることが不可欠です。したがって、 今回の研究の成果である新しい方法は、生物の基本的なメカニズムに関する知見が得られると期待されます。 さらに、分子の生物学的役割と機能についての深い知識は、さまざまな病気の原因と影響を理解するのに役立ちます。 高解像度の構造情報は、慢性および感染症の治療薬の開発に不可欠です。この研究は、私たちの基本的な生物学的知識を拡げ、新しい病気の治療法の開発を支援することにより、社会の幸福と生活の質の向上に貢献します。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • Research Products

    (16 results)

All 2020 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results) Presentation (10 results) (of which Int'l Joint Research: 3 results,  Invited: 9 results)

  • [Journal Article] Activation of the GLP-1 receptor by a non-peptidic agonist2020

    • Author(s)
      Zhao Peishen、Liang Yi-Lynn、Belousoff Matthew J.、Deganutti Giuseppe、Fletcher Madeleine M.、Willard Francis S.、Bell Michael G.、Christe Michael E.、Sloop Kyle W.、Inoue Asuka、Truong Tin T.、Clydesdale Lachlan、Furness Sebastian G. B.、Christopoulos Arthur、Wang Ming-Wei、et al
    • Journal Title

      Nature

      Volume: 577 Issue: 7790 Pages: 432-436

    • DOI

      10.1038/s41586-019-1902-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Toward a Structural Understanding of Class B GPCR Peptide Binding and Activation2020

    • Author(s)
      Liang Yi-Lynn、Belousoff Matthew J.、Zhao Peishen、Koole Cassandra、Fletcher Madeleine M.、Truong Tin T.、Julita Villy、Christopoulos George、Xu H. Eric、Zhang Yan、Khoshouei Maryam、Christopoulos Arthur、Danev Radostin、Sexton Patrick M.、Wootten Denise
    • Journal Title

      Molecular Cell

      Volume: 77 Issue: 3 Pages: 656-668.e5

    • DOI

      10.1016/j.molcel.2020.01.012

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Structure and Dynamics of Adrenomedullin Receptors AM1 and AM2 Reveal Key Mechanisms in the Control of Receptor Phenotype by Receptor Activity-Modifying Proteins2020

    • Author(s)
      Liang Yi-Lynn、Belousoff Matthew J.、Fletcher Madeleine M.、Zhang Xin、Khoshouei Maryam、Deganutti Giuseppe、Koole Cassandra、Furness Sebastian G. B.、Miller Laurence J.、Hay Debbie L.、Christopoulos Arthur、Reynolds Christopher A.、Danev Radostin、Wootten Denise、Sexton Patrick M.
    • Journal Title

      ACS Pharmacology & Translational Science

      Volume: 3 Issue: 2 Pages: 263-284

    • DOI

      10.1021/acsptsci.9b00080

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cryo-Electron Microscopy Methodology: Current Aspects and Future Directions2019

    • Author(s)
      Danev Radostin、Yanagisawa Haruaki、Kikkawa Masahide
    • Journal Title

      Trends in Biochemical Sciences

      Volume: 44 Issue: 10 Pages: 837-848

    • DOI

      10.1016/j.tibs.2019.04.008

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Improved applicability and robustness of fast cryo-electron tomography data acquisition2019

    • Author(s)
      Eisenstein Fabian、Danev Radostin、Pilhofer Martin
    • Journal Title

      Journal of Structural Biology

      Volume: 208 Issue: 2 Pages: 107-114

    • DOI

      10.1016/j.jsb.2019.08.006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cryo-EM Methodology: Current Aspects and Future Directions2019

    • Author(s)
      Radostin Danev, Haruaki Yanagisawa, Masahide Kikkawa
    • Journal Title

      Trends in Biochemical Sciences

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Phase plates in cryo-EM2019

    • Author(s)
      Radostin Danev
    • Organizer
      EMBL Cryo-EM in Industry and Academia workshop
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Practical Performance of the Volta Phase Plate2019

    • Author(s)
      Radostin Danev
    • Organizer
      Gordon Research Conference on Three Dimensional Electron Microscopy
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cryo-EM of Membrane Proteins With and Without Phase Plates2019

    • Author(s)
      Radostin Danev
    • Organizer
      71st joint JSCB and PSSJ meeting
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Cryo-EM of Membrane Receptors2019

    • Author(s)
      Radostin Danev
    • Organizer
      92nd annual meeting of the Japanese biochemical society
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Performance Contributions of Energy Filtering and Phase Plates for Single Particle Analysis of Membrane Proteins2019

    • Author(s)
      Radostin Danev
    • Organizer
      NIPS EM Workshop 2019
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] What makes a great cryo-EM?2019

    • Author(s)
      Radostin Danev
    • Organizer
      Future of Cryo-EM Developments Meeting
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Phase Plates in Cryo-EM2019

    • Author(s)
      Radostin Danev
    • Organizer
      EMBL Cryo-EM in Industry and Academia Workshop
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Electron Optics and Image Formation2019

    • Author(s)
      Radostin Danev
    • Organizer
      Cryo-Electron Microscopy Course at OIST
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Recent Cryo-EM Advancements2019

    • Author(s)
      Radostin Danev
    • Organizer
      1st Cryo-EM Network User Group Meeting
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Cryo-EM with and without phase plates2018

    • Author(s)
      Radostin Danev
    • Organizer
      Japanese Society of Microscopy Soft Materials Branch Meeting
    • Related Report
      2018 Annual Research Report
    • Invited

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Published: 2018-08-27   Modified: 2024-03-26  

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