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マラリア原虫の赤血球侵入関連分子分泌調節カスケードの解明

Research Project

Project/Area Number 17J09408
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Parasitology (including sanitary zoology)
Research InstitutionNagasaki University

Principal Investigator

石崎 隆弘  長崎大学, 医歯薬学総合研究科(医学系), 特別研究員(DC1)

Project Period (FY) 2017-04-26 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2019: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2018: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2017: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywords寄生虫学 / ネズミマラリア原虫 / 赤血球侵入 / シグナルカスケード / 遺伝子編集 / 誘導型遺伝子欠損 / シグナル経路
Outline of Annual Research Achievements

マラリア原虫の赤血球侵入は原虫の生存に必須なステップであり、宿主への病原性と密接な繋がりを持つ。赤血球から脱出した原虫はマイクロネームやロプトリーといった細胞小器官から種々の分子を順序立てて分泌しながら赤血球侵入を行う。マイクロネーム分子の分泌には細胞外液組成である低カリウム環境に曝露される事に起因するCa2+シグナルが関与することが明らかとなっているが、分子分泌に至るシグナル経路には不明な点が多い。本研究ではネズミマラリア原虫の後期シゾント期においてRNA発現が高いキナーゼ群を逆遺伝学的手法を用いて欠損させた原虫を用いて表現型解析を実施した。
網羅的に作製したキナーゼ欠損原虫(誘導型欠損原虫)の内、マイクロネーム分子の分泌が減少するキナーゼとマイクロネームとロプトリー分子の両方の分泌が減少するキナーゼの同定に成功したものの、同定したキナーゼによる分泌調節カスケードの全容は現在解析途中である。
また、本研究を通してネズミマラリア原虫のCRISPR/Cas9系、誘導型遺伝子欠損法(DiCre-loxP系)、並びに侵入関連分子分泌試験法を確立した。これら手法を駆使する事で赤血球侵入時におけるシグナル伝達を担う分子解析が可能となった。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research 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: 3 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (9 results) (of which Int'l Joint Research: 5 results)

  • [Int'l Joint Research] NIAID(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Umea University(スウェーデン)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Plasmodium yoelii Erythrocyte-Binding-like Protein Modulates Host Cell Membrane Structure, Immunity, and Disease Severity2020

    • Author(s)
      Peng Yu-chih、Qi Yanwei、Zhang Cui、Yao Xiangyu、Wu Jian、Pattaradilokrat Sittiporn、Xia Lu、Tumas Keyla C.、He Xiao、Ishizaki Takahiro、Qi Chen-Feng、Holder Anthony A.、Myers Timothy G.、Long Carole A.、Kaneko Osamu、Li Jian、Su Xin-zhuan
    • Journal Title

      mBio

      Volume: 11 Issue: 1

    • DOI

      10.1128/mbio.02995-19

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel Plasmodium yoelii pseudokinase, PypPK1, is involved in erythrocyte invasion and exflagellation center formation2020

    • Author(s)
      Ishizaki Takahiro、Chaiyawong Nattawat、Hakimi Hassan、Asada Masahito、Tachibana Mayumi、Ishino Tomoko、Yahata Kazuhide、Kaneko Osamu
    • Journal Title

      Parasitology International

      Volume: 76 Pages: 102056-102056

    • DOI

      10.1016/j.parint.2020.102056

    • NAID

      120006988309

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome editing of Babesia bovis using the CRISPR/Cas9 system.2019

    • Author(s)
      Hakimi, H., Ishizaki, T., Kegawa, Y., Kaneko, O., Kawazu, S., and Asada, M.
    • Journal Title

      mSphere

      Volume: 4(3) Issue: 3

    • DOI

      10.1128/msphere.00109-19

    • NAID

      120006988459

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Critical role of Erythrocyte Binding-Like protein of the rodent malaria parasite Plasmodium yoelii to establish an irreversible connection with the erythrocyte during invasion2018

    • Author(s)
      Kegawa Yuto、Asada Masahito、Ishizaki Takahiro、Yahata Kazuhide、Kaneko Osamu
    • Journal Title

      Parasitology International

      Volume: 67 Issue: 6 Pages: 706-714

    • DOI

      10.1016/j.parint.2018.07.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Babesia bovis BOV57, a Theileria parva P67 homolog, is an invasion-related, neutralization-sensitive antigen2017

    • Author(s)
      Ishizaki Takahiro、Sivakumar Thillaiampalam、Hayashida Kyoko、Takemae Hitoshi、Tuvshintulga Bumduuren、Munkhjargal Tserendorj、Guswanto Azirwan、Igarashi Ikuo、Yokoyama Naoaki
    • Journal Title

      Infection, Genetics and Evolution

      Volume: 54 Pages: 138-145

    • DOI

      10.1016/j.meegid.2017.06.025

    • NAID

      120006411414

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] A novel Plasmodium yoelii pseudokinase, PypPK1, is involved in erythrocyte invasion and exflagellation center formation2020

    • Author(s)
      Ishizaki T , Chaiyawong N , Hakimi H , Asada M , Tachibana M , Ishino T , Yahata K , Kaneko O
    • Organizer
      US-Japan Cooperative Medical Sciences Program: Parasitic Diseases Panel Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ネズミマラリア原虫Plasmodium yoeliiのdiacylglycerol kinase(DAGKp)は赤血球侵入関連分子の表面分泌に関わる2019

    • Author(s)
      石﨑隆弘 , 麻田正仁 , 徳舛富由樹 , 坂口美亜子 , 矢幡一英 , 金子修
    • Organizer
      第27回分子寄生虫学ワークショップ/第17回分子寄生虫・マラリア研究フォーラム合同大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A novel Plasmodium yoelii serine threonine kinase related to exflagellation center formation2019

    • Author(s)
      Ishizaki T., Chaiyawong N., Asada M., Yahata K., Culleton R., Kaneko O.
    • Organizer
      30th molecular parasitology meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ネズミマラリア原虫Plasmodium yoeliiのTgDAGK1ホモログPyDAGKpは侵入する赤血球選択性に関わる2019

    • Author(s)
      石﨑隆弘、麻田正仁、矢端一英、金子修
    • Organizer
      第88回日本寄生虫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Investigation of the erythrocyte invasion-related protein surface translocation in Plasmodium yoelii.2018

    • Author(s)
      Ishizaki T., Yahata K., Asada M., Kaneko O.
    • Organizer
      The 17th Awaji International Forum on infection and immunity
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dynamics of red blood cell invasion-related protein secretion in Plasmodium yoelii.2018

    • Author(s)
      Ishizaki T., Asada M., Yahata K., Kaneko O.
    • Organizer
      The 87th Annual Meeting of the Japanese Society of Parasitology
    • Related Report
      2017 Annual Research Report
  • [Presentation] EBL secretion dynamics of malaria parasites during erythrocyte invasion.2017

    • Author(s)
      Ishizaki T., Yahata K., Asada M., Kaneko O.
    • Organizer
      13th Nagasaki-Singapore Medical Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Erythrocyte binding-like protein is essential for the erythrocyte invasion by the rodent malaria parasite Plasmodium yoelii.2017

    • Author(s)
      Kegawa Y., Asada M., Ishizaki T., Yahata K., Kaneko O
    • Organizer
      The 16th Awaji International Forum on Infection and Immunity
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Secretion dynamics analysis of rodent malaria parasite, Plasmodium yoelii, during erythrocyte invasion2017

    • Author(s)
      Ishizaki T., Asada M., Yahata K., Kaneko O.
    • Organizer
      25th Molecular parasitology workshop
    • Related Report
      2017 Annual Research Report

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Published: 2017-05-25   Modified: 2024-03-26  

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