Analyses on membrane trafficking mechanism related to severe malaria

• Project/Area Number: 20H03476
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49040:Parasitology-related
• Research Institution: Tohoku University
• Principal Investigator: Kato Kentaro 東北大学, 農学研究科, 教授 (30401178)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2022: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2021: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2020: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: マラリア / メンブレントラフィック / ロゼット化 / シクエストレーション

Outline of Research at the Start

マラリア感染赤血球内で形作られる赤血球蛋白質や原虫蛋白質の輸送システム、赤血球膜に提示された蛋白質と宿主の血管内皮蛋白質との相互作用、というマラリアの病態発症や重症化に直接関わるメカニズムの解明についてはなおざりの状態である。本研究では、マラリアの病態の重症化の原因となる感染赤血球のロゼット化と血管内皮との癒着、結合（シクエストレーション）を担当する原虫蛋白質群や宿主細胞蛋白質群が、感染赤血球内でのメンブレントラフィックによって輸送され、感染赤血球膜に提示される機構の解明を目指す。

Outline of Final Research Achievements

The approach to study the malaria pathogenesis mechanism at the point of the interaction between Plasmodium and host erythrocytes has not been performed. The transportation system of erythrocyte and parasite proteins in Plasmodium-infected erythrocyte and the interaction between the erythrocyte surface proteins and vascular endothelium receptors are not clear. In this study we studied the membrane trafficking and presentation system to the erythrocyte surface for the proteins relating with rosette formation and binding and sequestration in vascular endothelium.

Academic Significance and Societal Importance of the Research Achievements

我々が独自に開発したマラリアの赤血球感染レセプター同定を行ってきた。次に、我々の研究の主題はマラリアの重症化機構の解明へと移行してきた。熱帯熱マラリアを重症化へと導く感染赤血球のロゼット化とシクエストレーションのメカニズムを明らかとすることは、すなわち多臓器不全によって致死に至るメカニズムを解き明かすことである。従って、本研究の成果は、死に至るステージを回避することができる新規の抗マラリア薬や未だ存在しないワクチンの開発に直接つながるため、学術的独自性があり、創造性の高いものである。

Research Products

• [Int'l Joint Research] UNIVERSITY OF RAJSHAHI(バングラデシュ)
• [Int'l Joint Research] Federal University Oye-Ekiti/Federal University of Technology(ナイジェリア)
• [Int'l Joint Research] UNIVERSITY OF RAJSHAHI(バングラデシュ)
• [Int'l Joint Research] Federal University Oye-Ekiti/Federal University of Technology(ナイジェリア)
• [Journal Article] Detection of Developmental Asexual Stage-Specific RNA Editing Events in Plasmodium falciparum 3D7 Malaria Parasite (2024)
  • Author(s): Azad Md Thoufic Anam、Sugi Tatsuki、Qulsum Umme、Kato Kentaro
  • Journal Title: Microorganisms Volume: 12 Issue: 1 Pages: 137-137
  • DOI: 10.3390/microorganisms12010137
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Antiplasmodial and interferon-gamma-modulating activities of the aqueous extract of stone breaker (Phyllanthus niruri Linn.) in malaria infection (2023)
  • Author(s): Jeje Temitope Olawale、Bando Hironori、Azad Md Thoufic Anam、Fukuda Yasuhiro、Oluwafemi Ibukun Emmanuel、Kato Kentaro
  • Journal Title: Parasitology International Volume: 97 Pages: 102789-102789
  • DOI: 10.1016/j.parint.2023.102789
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The Efficacy of Marine Natural Products Against Plasmodium falciparum (2021)
  • Author(s): Goto Yukihiro、Kamihira Rie、Nakao Yoichi、Nonaka Motohiro、Takano Ryo、Xuan Xuenan、Kato Kentaro
  • Journal Title: Journal of Parasitology Volume: 107 Issue: 2 Pages: 284-288
  • DOI: 10.1645/20-93
  • Peer Reviewed / Open Access
• [Journal Article] Tree of motility : A proposed history of motility systems in the tree of life (2020)
  • Author(s): M Miyata, R C Robinson, T QP Uyeda, Y Fukumori, S Fukushima, S Haruta, M Homma, K Inaba, M Ito, C Kaito, K Kato, TKenri, Y Kinosita, S Kojima, T Minamino, H Mori, S Nakamura, D Nakane, K Nakayama, M Nishiyama, S Shibata, K Shimabukuro, M Tamakoshi, A Taoka, Y Tashiro, ITulum, HiWada, K Wakabayashi
  • Journal Title: Genes to Cells Volume: 25 Issue: 1 Pages: 6-21
  • DOI: 10.1111/gtc.12737
  • NAID: 130007881664
  • URL: https://ocu-omu.repo.nii.ac.jp/records/2019864
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] In vitro antiplasmodial activity of nine selected traditional medicinal plants from Bangladesh (2024)
  • Author(s): Umme Qulsum, Md Thoufic Anam Azad, Kentaro Kato.
  • Organizer: 第93回日本寄生虫学会
• [Presentation] Genome-wide detection of conserved stage-specific RNA editing events for nuclear genes in P. falciparum 3D7 malaria parasite (2024)
  • Author(s): Azad Md Thoufic Anam, Tatsuki Sugi, Kentaro Kato.
  • Organizer: 第93回日本寄生虫学会
• [Presentation] Detection of developmental stage specific RNA editing events in 28S ribosomal RNA gene of Plasmodium falciparum (2023)
  • Author(s): Md Thoufic Anam Azad, Kentaro Kato.
  • Organizer: 第92回日本寄生虫学会
• [Presentation] Efficacy of the medicinal plants and their derived biomolecules against apicomplexan pathogen (2023)
  • Author(s): Umme Qulsum, Kentaro Kato.
  • Organizer: 第69回日本寄生虫学会・日本衛生動物学会 北日本支部合同大会
• [Presentation] Genome-wide detection of stage-specific RNA editing events for nuclear genes in P. falciparum 3D7 malaria parasite (2023)
  • Author(s): Azad Md Thoufic Anam, Tatsuki Sugi, Kentaro Kato.
  • Organizer: 第69回日本寄生虫学会・日本衛生動物学会 北日本支部合同大会
• [Presentation] Detection of developmental stage specific RNA editing events in 28s ribosomal RNA gene of Plasmodium falciparum (2023)
  • Author(s): Azad Md Thoufic Anam, Kentaro Kato
  • Organizer: 第92回日本寄生虫学会
• [Presentation] The pathogenesis and clinical manifestations of and anti-parasitic drug development for malaria and toxoplasmosis (2021)
  • Author(s): Kentaro Kato
  • Organizer: The symposium of the Korean society for parasitology 2021
  • Invited
• [Presentation] Phyllanthus niruri protects against severe malaria by blocking erythrocyte invasion (2021)
  • Author(s): 加藤健太郎、Jeje Temitope、伴戸寛徳、福田康弘
  • Organizer: 第164回日本獣医学会学術集会
• [Presentation] Phyllanthus niruri protects against severe malaria by blocking erythrocyte invasion and modulating the host immune response (2021)
  • Author(s): 加藤健太郎、Temitope Jeje、伴戸寛徳、福田康弘
  • Organizer: 第90回日本寄生虫学会
• [Presentation] Aqueous extract of Phyllanthus niruri protects against severe malaria by blocking erythrocyte invasion (2020)
  • Author(s): Temitope Jeje、伴戸寛徳、福田康弘、加藤健太郎
  • Organizer: 第163回日本獣医学会学術集会
• [Presentation] Assessment of anti-protozoan activity of some African plant extracts (2020)
  • Author(s): Jeje Temitope、伴戸寛徳、加藤健太郎
  • Organizer: 第89回日本寄生虫学会大会
• [Presentation] Proteomic Dissection of Plasmodium falciparum Maurer's cleft Compartments Using SBP1 (2020)
  • Author(s): Kentaro KATO, Ryo TAKANO, Hiroko KOZUKA-HATA, Daisuke KONDOH, Hiroki BOCHIMOTO, Masaaki OYAMA
  • Organizer: The 17th International Symposium on Integrated Field Science
  • Int'l Joint Research / Invited
• [Presentation] A multifaceted analysis of the effect of medicinal plant Phyllanthus ninuri on the improvement of severe malaria (2020)
  • Author(s): Temitope Jeje, Hironori Bando, Yasuhiro Fukuda, Kentaro Kato
  • Organizer: The 17th International Symposium on Integrated Field Science
  • Int'l Joint Research
• [Remarks] 東北大学大学院農学研究科動物環境管理学分野のホームページ
  • URL: https://www.agri.tohoku.ac.jp/health/index.html
• [Patent(Industrial Property Rights)] 抗マラリア薬 (2024)
  • Inventor(s): 加藤健太郎、クルスム ウメ
  • Industrial Property Rights Holder: 加藤健太郎、クルスム ウメ
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2024-067382
  • Filing Date: 2024
• [Patent(Industrial Property Rights)] マラリア原虫の赤血球への侵入阻害剤 (2020)
  • Inventor(s): 加藤健太郎、伴戸寛徳、オラワレ ジェジェ
  • Industrial Property Rights Holder: 加藤健太郎、伴戸寛徳、オラワレ ジェジェ
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2020-147434
  • Filing Date: 2020