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Signaling in malaria parasites during erythrocyte invasion

Research Project

Project/Area Number 16H05184
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Parasitology (including sanitary zoology)
Research InstitutionNagasaki University

Principal Investigator

KANEKO Osamu  長崎大学, 熱帯医学研究所, 教授 (50325370)

Co-Investigator(Kenkyū-buntansha) 矢幡 一英  長崎大学, 熱帯医学研究所, 助教 (40467965)
麻田 正仁  帯広畜産大学, 原虫病研究センター, 准教授 (40587028)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywords原虫 / マラリア / 細胞侵入 / シグナル伝達
Outline of Final Research Achievements

Erythrocyte invasion is an essential step for malaria parasites, however, its intracellular signaling is not fully understood. To gain further insights of such signaling mechanism, we generated and analyzed a panel of transgenic rodent malaria parasite Plasmodium yoelii, in which the expression of target proteins can be inducibly silenced. We identified several kinases are essential during erythrocyte invasion and one pseudokinases has a role at sexual stage in the mosquitoes in addition to a role during erythrocyte invasion. We also visualized that the parasite could not tightly bind to the eryrhrocyte when a parasite ligand called EBL was silenced. Lastly, we gained a new insight about the virulence of P. yoelii.

Academic Significance and Societal Importance of the Research Achievements

マラリア原虫は人体内で増殖するために赤血球へ侵入しなくてはならない。そのため、赤血球侵入期原虫に発現する分子はワクチンや薬剤開発の標的と考えられる。本研究では、ネズミマラリア原虫P. yoeliiを用いて、赤血球侵入期に発現する複数の原虫リン酸化酵素が原虫に必須であることを明らかにし、これらを標的とする薬剤により原虫を殺滅させることができる可能性を示した。また、本研究で開発したP. yoeliiの遺伝子改変・編集の技術や動画解析法、病原性に関する新知見などの情報を研究者コミュニティに提供することで、マラリア研究への貢献ができた。

Report

(4 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (39 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (9 results) Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (26 results) (of which Int'l Joint Research: 14 results,  Invited: 1 results)

  • [Int'l Joint Research] Kangwon National University(韓国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] NIAID, NIH(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] The Francis Crick Institute(英国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Edinburgh/Wellcome Trust Sanger Institute/University of Cambridge(英国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] KAUST(サウジアラビア)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Mount Kenya University(ケニア)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Jiangsu Institute of Parasitic Diseases(中国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] NIAID, NIH(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research]

    • Related Report
      2017 Annual Research Report
  • [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] Fragment Molecular Orbital Study of the Interaction between Sarco/Endoplasmic Reticulum Ca2+-ATPase and its Inhibitor Thapsigargin toward Anti-Malarial Development2018

    • Author(s)
      Ishikawa Takeshi、Mizuta Satoshi、Kaneko Osamu、Yahata Kazuhide
    • Journal Title

      The Journal of Physical Chemistry B

      Volume: 122 Issue: 33 Pages: 7970-7977

    • DOI

      10.1021/acs.jpcb.8b04509

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cross-species analysis of apical asparagine-rich protein of Plasmodium vivax and Plasmodium knowlesi2018

    • Author(s)
      Muh Fauzi、Ahmed Md Atique、Han Jin-Hee、Nyunt Myat Htut、Lee Seong-Kyun、Lau Yee Ling、Kaneko Osamu、Han Eun-Taek
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 5781-5781

    • DOI

      10.1038/s41598-018-23728-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rapid identification of genes controlling virulence and immunity in malaria parasites2017

    • Author(s)
      Abkallo HM, Martinelli A, Inoue M, Ramaprasad A, Xangsayarath P, Gitaka J, Tang J, Yahata K, Zoungrana A, Mitaka H, Acharjee A, Datta PP, Hunt P, Carter R, Kaneko O, Mustonen V, Illingworth CJR, Pain A, Culleton R
    • Journal Title

      PLOS Pathogens

      Volume: 13 Issue: 7 Pages: e1006447-e1006447

    • DOI

      10.1371/journal.ppat.1006447

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Erythrocyte-Binding-Like protein of Plasmodium yoelii is critical for the erythrocyte invasion2019

    • Author(s)
      Kegawa Y, Asada M, Ishizaki T, Yahata K, Kaneko O
    • Organizer
      US-Japan Cooperative Medical Sciences Program: Parasitic Disease joint meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ネズミマラリア原虫 Plasmodium yoelii の新規セリンスレオニンキナーゼ及びTgDGK1 ホモログ PyDAGKp は侵入する赤血球選択性に関与する2019

    • Author(s)
      石﨑隆弘, 麻田正仁, 矢幡一英, 金子修
    • Organizer
      第88回日本寄生虫学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Gliding motility of Plasmodium merozoites2019

    • Author(s)
      Yahata K
    • Organizer
      NUS-NU Joint Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マラリア原虫メロゾイトの滑走運動2019

    • Author(s)
      矢幡一英, Davies H, 麻田正仁, Templeton T, Treeck M, 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
      2018 Annual Research Report
  • [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
      2018 Annual Research Report
  • [Presentation] Uncovering the mechanism of erythrocyte invasion through phenotypic characterization of undefined malaria parasite proteins for their roles in host cell invasion2019

    • Author(s)
      Suzuki M, Ishizaki T, Asada M, Yahata K, Kaneko O
    • 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
      2018 Annual Research Report
  • [Presentation] Characterizing actin-binding behaviors of malaria parasite actin depolymerizing factor2019

    • Author(s)
      Suzuki M, Yahata K, Kaneko O, Uyeda TQP
    • Organizer
      The 18th Awaji International Forum on Infection and Immunity
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization of a novel Plasmodium yoelii serine threonine kinase related to exflagellation center formation2019

    • Author(s)
      Ishizaki T, Chaiyawong N, Tachibana M, Ishino T, Yahata K, Asada M, Kaneko O
    • Organizer
      The 18th Awaji International Forum on Infection and Immunity
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [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 Annual Molecular Parasitology Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular signaling during RBC invasion by malaria parasites2018

    • Author(s)
      Yahata K, Asada M, Kaneko O
    • Organizer
      20th Forum Cheju
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of factor(s) that determine growth rate and virulence in the rodent malaria parasite Plamodium yoelii2018

    • Author(s)
      Chaiyawong N, Asada M, Medard E, Yahata K, Yamagishi J, Culleton R, Kaneko O
    • Organizer
      The 17th Awaji International Forum on Infection and Immunity
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Distinct timing of secretion of the erythrocyte invasion-related molecules from Plasmodium yoelii merozoite2018

    • Author(s)
      Ishizaki T, Asada M, Yahata K, Kaneko O
    • Organizer
      The 17th Awaji International Forum on Infection and Immunity
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Critical role of Erythrocyte Binding-Like protein of the rodent malaria parasite Plasmodium yoelii to establish an irreversible connection with the erythrocyte during the invasion2018

    • Author(s)
      Kegawa Y, Asada M, Ishizaki T, Yahata K, Kaneko O
    • Organizer
      The 17th Awaji International Forum on Infection and Immunity
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Erythrocyte binding-like protein is essential for the erythrocyte invasion by the rodent malaria parasite Plasmodium yoelii2018

    • Author(s)
      Kegawa Y, Asada M, Ishizaki T, Yahata K, Kaneko O
    • Organizer
      Forum Cheju 19
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ネズミマラリア原虫を用いた赤血球侵入関連分子分泌動態2018

    • Author(s)
      石﨑隆弘、麻田正仁、矢幡一英、金子修
    • Organizer
      第87回日本寄生虫学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Plasmodium yoeliiのErythrocyte-Binding-Like(EBL)タンパク質は赤血球侵入に必須である2018

    • Author(s)
      外川裕人、麻田正仁、石崎隆弘、矢幡一英、金子修
    • Organizer
      第87回日本寄生虫学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Erythrocyte binding-like protein is essential for the erythrocyte invasion by the rodent malaria parasite Plasmodium yoelii2017

    • Author(s)
      Kegawa Y, Asada M, Yahata K, Kaneko O
    • Organizer
      The 13th Nagasaki-Singapore Medical Symposium / Leading Program International Symposium 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Plasmodium yoelii erythrocyte-binding-like (EBL) 遺伝子は赤血球侵入に必須である2017

    • Author(s)
      外川裕人、麻田正仁、矢幡一英、金子修
    • Organizer
      第86回日本寄生虫学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ネズミマラリア原虫赤血球侵入関連分子分泌動態の解析2017

    • Author(s)
      石崎隆弘、麻田正仁、矢幡一英、金子修
    • Organizer
      第25回分子寄生虫学ワークショップ/第15回分子寄生虫・マラリア研究フォーラム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Erythrocyte binding-like protein is essential for the erythrocyte invasion by the rodent malaria parasite Plasmodium yoelii2017

    • Author(s)
      Kegawa Y, Asada M, 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] Rapid identification of genes controlling major phenotypes in malaria parasites using a genomics-driven Linkage Group Selection (LGS) approach2017

    • Author(s)
      Abkallo HM, Martinelli A, Inoue M, Hayashida K, Sugimoto C, Kaneko O, Illingworth CJR, Pain A, Culleton R
    • Organizer
      The 16th Awaji International Forum on Infection and Immunity
    • 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 yoelii2017

    • Author(s)
      Kegawa Y, Asada M, Yahata K, Kaneko O
    • Organizer
      2017 (28th) Annual Molecular Parasitology Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マラリア原虫の赤血球侵入2017

    • Author(s)
      金子修
    • Organizer
      第73回日本寄生虫学会西日本支部大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Development of Tet-On-Cre/loxP conditional gene knockout system for rodent malaria parasite Plasmodium yoelii2016

    • Author(s)
      Asada M, Kegawa Y, Yahata K, Kaneko O
    • Organizer
      第5回感染症若手フォーラム
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫県淡路市)
    • Year and Date
      2016-09-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] マラリア原虫赤血球侵入関連分子分泌調節を担うキナーゼの同定2016

    • Author(s)
      石﨑隆弘、麻田正仁、外川裕人、矢幡一英、金子修
    • Organizer
      第24回分子寄生虫学ワークショップ/第14回分子寄生虫・マラリア研究フォーラム
    • Place of Presentation
      帯広畜産大学(北海道帯広市)
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] Plasmodium yoeliiにおけるテトラサイクリン発現誘導システム(Tet-Offシステム)の確立とその応用2016

    • Author(s)
      外川裕人、麻田正仁、矢幡一英、金子修
    • Organizer
      第24回分子寄生虫学ワークショップ/第14回分子寄生虫・マラリア研究フォーラム
    • Place of Presentation
      帯広畜産大学(北海道帯広市)
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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