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Evaluation of the mechanism for erythrocyte-invasion through the targetome analyses in the Plasmodium merozoite stage

Research Project

Project/Area Number 21K06986
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49040:Parasitology-related
Research InstitutionMie University

Principal Investigator

Nishi Tsubasa  三重大学, 医学系研究科, 助教 (50880051)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsマラリア原虫 / 遺伝子転写制御機構 / メロゾイト / ターゲトーム / 侵入・感染
Outline of Research at the Start

マラリア原虫のメロゾイトは赤血球への侵入・感染を行う極めて重要な細胞ステージである。申請者はこれまでに、メロゾイト形成期に必須である3種のAP2ファミリー転写因子を発見した。そして、これらの転写因子の標的遺伝子解析から、マラリア原虫メロゾイト形成の分子基盤を理解するうえで非常に有力な情報が得られることを構想した。本研究の成果は、生物学基礎研究の発展のみならず、新たな薬剤・ワクチン標的候補遺伝子発見にもつながり、その波及効果は極めて大きいものとなる。

Outline of Final Research Achievements

In this study, we investigated the function of three AP2-family transcription factors that are specifically expressed during the merozoite formation in Plasmodium berghei. We revealed that the three transcription factors generate the cascade of gene transcription to regulate the merozoite formation in several steps, such as karyokinesis, cytokinesis, and formation of invasion-related organelles. Our data are not only important for evaluating the transcriptional regulation that underlies the Plasmodium merozoite formation but also contribute to the studies that aim to identify new candidates for malaria vaccine targets.

Academic Significance and Societal Importance of the Research Achievements

マラリアは三大感染症の一つであり、現在も途上国を中心に年間約2億人の罹患者、60万人を超える死者が報告されている。本研究の成果は、マラリアの病原体であるPlasmodium属原虫の赤血球侵入ステージであるメロゾイトについて、深い理解を与えるものである。また、原虫の赤血球ステージはその病原性に直接かかわっており、特にメロゾイトは細胞侵入ステージであることから、マラリアワクチンにおける魅力的な標的とされる。よって、本研究のメロゾイト形成期における標的遺伝子解析の結果は、新たなワクチン標的分子の探索においても非常に有力な情報となる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (8 results)

All 2024 2023 2022

All Journal Article (6 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (2 results)

  • [Journal Article] PbARID-associated chromatin remodeling events are essential for gametocyte development in Plasmodium2024

    • Author(s)
      Nishi Tsubasa、Kaneko Izumi、Iwanaga Shiroh、Yuda Masao
    • Journal Title

      Nucleic Acids Research

      Volume: - Issue: 10 Pages: 1-19

    • DOI

      10.1093/nar/gkae207

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Coordinated regulation of gene expression in Plasmodium female gametocytes by two transcription factors2024

    • Author(s)
      Murata Yuho、Nishi Tsubasa、Kaneko Izumi、Iwanaga Shiroh、Yuda Masao
    • Journal Title

      eLife

      Volume: 12 Pages: 1-9

    • DOI

      10.7554/elife.88317

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differentiation of Plasmodium male gametocytes is initiated by the recruitment of a chromatin remodeler to a male-specific cis-element2023

    • Author(s)
      Kaneko Izumi、Nishi Tsubasa、Iwanaga Shiroh、Yuda Masao
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 120 Issue: 20 Pages: 2303432120-2303432120

    • DOI

      10.1073/pnas.2303432120

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Toxoplasma IWS1 Determines Fitness in Interferon-γ-Activated Host Cells and Mice by Indirectly Regulating ROP18 mRNA Expression.2023

    • Author(s)
      Hashizaki Emi、Sasai Miwa、Okuzaki Daisuke、Nishi Tsubasa、Kobayashi Takashi、Iwanaga Shiroh、Yamamoto Masahiro
    • Journal Title

      mBio

      Volume: 14 Issue: 1

    • DOI

      10.1128/mbio.03256-22

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PbAP2-FG2 and PbAP2R-2 function together as a transcriptional repressor complex essential for Plasmodium female development2023

    • Author(s)
      Nishi Tsubasa、Kaneko Izumi、Iwanaga Shiroh、Yuda Masao
    • Journal Title

      PLOS Pathogens

      Volume: 19 Issue: 2 Pages: 1010890-1010890

    • DOI

      10.1371/journal.ppat.1010890

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of a novel AP2 transcription factor in zygotes with an essential role in Plasmodium ookinete development2022

    • Author(s)
      Nishi Tsubasa、Kaneko Izumi、Iwanaga Shiroh、Yuda Masao
    • Journal Title

      PLOS Pathogens

      Volume: 18 Issue: 8 Pages: 1010510-1010510

    • DOI

      10.1371/journal.ppat.1010510

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] マラリア原虫雄性生殖母体形成におけるクロマチンリモデリング因子gSNF2とPbARIDの役割2024

    • Author(s)
      西 翔、金子 伊澄、岩永 史郎、油田 正夫
    • Organizer
      第93回日本寄生虫学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] RIME法によるマラリア原虫雌性生殖母体特異的転写因子AP2-FG2のコファクターの同定2023

    • Author(s)
      西翔、金子伊澄、岩永史朗、油田正夫
    • Organizer
      日本寄生虫学会大会
    • Related Report
      2022 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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