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Comprehensive analyses of RBC-malaria parasite PPI interactome

Research Project

Project/Area Number 20H03481
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49040:Parasitology-related
Research InstitutionEhime University

Principal Investigator

Tsuboi Takafumi  愛媛大学, プロテオサイエンスセンター, 特命教授 (00188616)

Co-Investigator(Kenkyū-buntansha) 竹田 浩之  愛媛大学, プロテオサイエンスセンター, 准教授 (40609393)
高島 英造  愛媛大学, プロテオサイエンスセンター, 准教授 (50366762)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2022: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2021: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2020: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Keywordsマラリア原虫 / 赤血球 / タンパク質 / インタラクトーム / ワクチン
Outline of Research at the Start

マラリアは熱帯地域で流行し多くの人命を奪っている感染症で、マラリア原虫が赤血球へ侵入し発育することが病気の本態ですが、その分子メカニズムはほとんど判っていません。本研究では、申請者らが世界に先駆けて開発した新技術を用いて、マラリア原虫とヒト赤血球のタンパク質-タンパク質相互作用を全て解明することにより、マラリア原虫の赤血球への侵入や赤血球内での原虫発育の分子メカニズムを解明します。その結果、マラリアという病気の仕組みが分子レベルで判り、ひいてはマラリアを制圧するためのワクチンや薬剤開発につながります。

Outline of Final Research Achievements

Understanding the protein-protein interactions (PPI) between malaria parasite and its host is essential for vaccine and drug development. This study focused on the asexual blood-stage malaria, the main battleground of malaria disease, and aimed to elucidate the PPI between merozoites and erythrocytes. First, we elucidated the PPI of the malaria merozoite protein EBL and the erythrocyte protein and discovered an erythrocyte receptor. Next, we hypothesized that if we could inhibit the PPI between parasites and erythrocytes, we could proceed to develop a novel malaria vaccine. We found that inhibiting the function of PfRipr5, a merozoite invasion-related protein that binds to receptors on the erythrocyte surface, would pave the way for the development of a novel malaria vaccine.

Academic Significance and Societal Importance of the Research Achievements

本研究により、赤血球期におけるマラリア原虫と赤血球のタンパク質間PPIデータが得られ、赤血球期マラリアで生起する宿主-寄生体分子機構の一端を明らかにすることができた。したがって、本研究をさらに進展させれば、赤血球期マラリア原虫にとっての「アキレス腱」となる原虫タンパク質や赤血球レセプターの同定は勿論、これらのPPIをターゲットとした新規抗マラリア薬及びワクチンの開発にも発展することが期待できる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (49 results)

All 2022 2021 2020 Other

All Int'l Joint Research (15 results) Journal Article (12 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 12 results,  Open Access: 12 results) Presentation (19 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Remarks (3 results)

  • [Int'l Joint Research] WEHI/Burnet Institute/University of Melbourne(オーストラリア)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] iBET(ポルトガル)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] EVI(ドイツ)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] State University of New York/NIAID/PATH(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Institut Pasteur(フランス)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research]

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] PATH/NIAID/State University of New York(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] EVI(ドイツ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] iBET(ポルトガル)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] WEHI/Burnet Institute/University of Melbourne(オーストラリア)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Mahidol University(タイ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] PATH/State University of New York/University of Pennsylvania(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] EVI(ドイツ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] iBET(ポルトガル)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Mahidol University(タイ)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Naturally acquired antibody kinetics against Plasmodium vivax antigens in people from a low malaria transmission region in western Thailand2022

    • Author(s)
      Liu Zoe Shih-Jung、Sattabongkot Jetsumon、White Michael、Chotirat Sadudee、Kumpitak Chalermpon、Takashima Eizo、Harbers Matthias、Tham Wai-Hong、Healer Julie、Chitnis Chetan E.、Tsuboi Takafumi、Mueller Ivo、Longley Rhea J.
    • Journal Title

      BMC Medicine

      Volume: 20 Issue: 1 Pages: 89-89

    • DOI

      10.1186/s12916-022-02281-9

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Plasmodium vivax malaria serological exposure markers: Assessing the degree and implications of cross-reactivity with P.?knowlesi2022

    • Author(s)
      Longley Rhea J.、Grigg Matthew J.、Schoffer Kael、Obadia Thomas、Hyslop Stephanie、Piera Kim A.、Nekkab Narimane、Mazhari Ramin、Takashima Eizo、et al
    • Journal Title

      Cell Reports Medicine

      Volume: 3 Issue: 6 Pages: 100662-100662

    • DOI

      10.1016/j.xcrm.2022.100662

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Asexual Blood-Stage Malaria Vaccine Candidate PfRipr5: Enhanced Production in Insect Cells2022

    • Author(s)
      Correia Ricardo、Fernandes B、Castro Rute、Nagaoka Hikaru、Takashima Eizo、Tsuboi Takafumi、Fukushima Akihisa、Viebig Nicola K.、Depraetere Hilde、Alves Paula M.、Rold?o Ant?nio
    • Journal Title

      Frontiers in Bioengineering and Biotechnology

      Volume: 10 Pages: 908509-908509

    • DOI

      10.3389/fbioe.2022.908509

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Meta-Analysis of Human Antibodies Against Plasmodium falciparum Variable Surface and Merozoite Stage Antigens2022

    • Author(s)
      Takashima Eizo、Kanoi Bernard N.、Nagaoka Hikaru、Morita Masayuki、Hassan Ifra、Palacpac Nirianne M. Q.、Egwang Thomas G.、Horii Toshihiro、Gitaka Jesse、Tsuboi Takafumi
    • Journal Title

      Frontiers in Immunology

      Volume: 13 Pages: 887219-887219

    • DOI

      10.3389/fimmu.2022.887219

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vaccine co-display of CSP and Pfs230 on liposomes targeting two Plasmodium falciparum differentiation stages2022

    • Author(s)
      Huang Wei-Chiao、Mabrouk Moustafa T.、Zhou Luwen、Baba Minami、Tachibana Mayumi、Torii Motomi、Takashima Eizo、Locke Emily、Plieskatt Jordan、King C. Richter、Coelho Camila H.、Duffy Patrick E.、Long Carole、Tsuboi Takafumi、Miura Kazutoyo、Wu Yimin、Ishino Tomoko、Lovell Jonathan F.
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 773-773

    • DOI

      10.1038/s42003-022-03688-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Assessment of IgG3 as a serological exposure marker for Plasmodium vivax in areas with moderate?high malaria transmission intensity2022

    • Author(s)
      Tayipto Yanie、Rosado Jason、Gamboa Dionicia、White Michael T.、Kiniboro Benson、Healer Julie、Opi D. Herbert、Beeson James G.、Takashima Eizo、Tsuboi Takafumi、Harbers Matthias、Robinson Leanne、Mueller Ivo、Longley Rhea J.
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 12 Pages: 50909-50909

    • DOI

      10.3389/fcimb.2022.950909

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel asexual blood-stage malaria vaccine candidate: PfRipr5 formulated with human-use adjuvants induces potent growth inhibitory antibodies2022

    • Author(s)
      Takashima Eizo、Nagaoka Hikaru、Correia Ricardo、Alves Paula M.、Rold?o Ant?nio、Christensen Dennis、Guderian Jeffrey A.、Fukushima Akihisa、Viebig Nicola K.、Depraetere Hilde、Tsuboi Takafumi
    • Journal Title

      Frontiers in Immunology

      Volume: 13 Pages: 1002430-1002430

    • DOI

      10.3389/fimmu.2022.1002430

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison of Antibody Responses and Parasite Clearance in Artemisinin Therapeutic Efficacy Studies in the Democratic Republic of Congo and Asia2022

    • Author(s)
      Cutts Julia C、O’Flaherty Katherine、Takashima Eizo、Tsuboi Takafumi、et al
    • Journal Title

      The Journal of Infectious Diseases

      Volume: 226 Issue: 2 Pages: 324-331

    • DOI

      10.1093/infdis/jiac232

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Plasmodium falciparum SURFIN4.1 forms an intermediate complex with PTEX components and Pf113 during export to the red blood cell2021

    • Author(s)
      Miyazaki Shinya、Chitama Ben-Yeddy Abel、Kagaya Wataru、Lucky Amuza Byaruhanga、Zhu Xiaotong、Yahata Kazuhide、Morita Masayuki、Takashima Eizo、Tsuboi Takafumi、Kaneko Osamu
    • Journal Title

      Parasitology International

      Volume: 83 Pages: 102358-102358

    • DOI

      10.1016/j.parint.2021.102358

    • NAID

      120007166820

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] AGIA Tag System for Ultrastructural Protein Localization Analysis in Blood-Stage Plasmodium falciparum2021

    • Author(s)
      Morita Masayuki、Kanoi Bernard N.、Shinzawa Naoaki、Kubota Rie、Takeda Hiroyuki、Sawasaki Tatsuya、Tsuboi Takafumi、Takashima Eizo
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 11 Pages: 777291-777291

    • DOI

      10.3389/fcimb.2021.777291

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of a Novel RAMA/RON3 Rhoptry Protein Complex in Plasmodium falciparum Merozoites2021

    • Author(s)
      Ito Daisuke、Chen Jun-Hu、Takashima Eizo、Hasegawa Tomoyuki、Otsuki Hitoshi、Takeo Satoru、Thongkukiatkul Amporn、Han Eun-Taek、Tsuboi Takafumi
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 10 Pages: 296-296

    • DOI

      10.3389/fcimb.2020.605367

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Plasmodium yoelii erythrocyte binding like protein interacts with basigin, an erythrocyte surface protein2021

    • Author(s)
      Yuguchi T, Kanoi BN, Nagaoka H, Miura T, Ito D, Takeda H, Tsuboi T, Takashima E, Otsuki H
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: In press

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Plasmodium falciparum vaccine candidate discovery leveraged by wheat germ cell-free system2022

    • Author(s)
      Takashima E, Nagaoka H, Kanoi B, Morita M, Fukushima A, Miura K, Tsuboi T
    • Organizer
      The 20th Protein Island Matsuyama (PIM) International Symposium
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PfRipr5, a novel blood-stage malaria vaccine candidate, formulated with adjuvants for human use, induced potent growth inhibitory antibodies2022

    • Author(s)
      Takashima E, Nagaoka H, Correia R, Roldao A, Fukushima A, Viebig N, Tsuboi T
    • Organizer
      ASTMH 71st annual meeting
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ultrastructual localization analysis of Plasmodium falciparum proteins using AGIA tag system2022

    • Author(s)
      Morita M, Kanoi B, Shinzawa N, Takeda H, Sawasaki T, Tsuboi T, Takashima E
    • Organizer
      The 20th Protein Island Matsuyama (PIM) International Symposium
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ultrastructual localization analysis of Plasmodium falciparum merozoite proteins using AGIA tag-monoclonal antibody system2022

    • Author(s)
      Morita M, Kanoi B, Shinzawa N, Kubota R, Takeda H, Sawasaki T, Tsuboi T, Takashima E
    • Organizer
      International Congress of Parasitology (ICOPA) 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 熱帯熱マラリア原虫感染赤血球 VSA 網羅的タンパク質ライブラリーによる防御抗 原の探索2022

    • Author(s)
      高島英造、カノイ バーナード、坪井敬文
    • Organizer
      第91回日本寄生虫学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 熱帯熱マラリア原虫メロゾイト侵入機構解明に向けた原虫増殖活性を有する抗 Riprモノクローナル抗体の作出2022

    • Author(s)
      長岡ひかる、福島晃久、坪井敬文、高島英造
    • Organizer
      第91回日本寄生虫学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] AGIA タグシステムによるマラリア原虫タンパク質の超微細局在解析2022

    • Author(s)
      森田将之、カノイ バーナード、新澤直明、窪田理恵、竹田浩之、澤崎達也、坪井敬文、高島英造
    • Organizer
      第91回日本寄生虫学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 熱帯熱マラリア原虫生殖母体期における PTEX 複合体構成タンパク質の発現プロファイル解析2022

    • Author(s)
      岡田小夏、伊坂 恵里奈、面田彩馨、吉野健一、石野智子、橘 真由美、鳥居本美、高島英造、坪井敬文、入子英幸
    • Organizer
      第91回日本寄生虫学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] コムギ無細胞系による三日熱マラリアヒプノゾイト血清診断マーカーの開発と検証2021

    • Author(s)
      高島英造、坪井敬文、森田将之、 Longley Rhea、 White Michael、Harbes Matthias、 Ding Xavier、 Mueller Ivo
    • Organizer
      第90回日本寄生虫学会・第32回日本臨床寄生虫学会合同大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 赤血球期熱帯熱マラリア原虫 PHISTcタンパク質Pf3D7_0801000の性状解析2021

    • Author(s)
      長岡ひかる、カノイ バーナード、森田将之、中田貴敬、ニリアン パラクパック、堀井俊宏、坪井敬文、高島英造
    • Organizer
      第90回日本寄生虫学会・第32回日本臨床寄生虫学会合同大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] マラリア原虫メロゾイトのデンスグラニュール分子LSA3の赤血球寄生における機能解析2021

    • Author(s)
      森田将之、 Jennison Charlie、石野智子、 O'Neill Matthew、Boddey Justin A.、鳥居本美、坪井敬文、高島英造
    • Organizer
      第90回日本寄生虫学会・第32回日本臨床寄生虫学会合同大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Isentification of a novel RAMA/RON3 rhoptry protein complex in Plasmodium falciparum merozoites2021

    • Author(s)
      伊藤大輔、Chen jun-Hu、高島英造、長谷川倫之、大槻均、竹尾暁、Thongkukiatkul、HanEun-Taek、坪井敬文
    • Organizer
      第90回日本寄生虫学会・第32回日本臨床寄生虫学会合同大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 熱帯熱マラリア原虫の生殖母体期における原虫タンパク質輸送機構の解析2021

    • Author(s)
      面田彩馨、橘 真由美、石野智子、鳥居本美、坪井敬文、入子英幸
    • Organizer
      第90回日本寄生虫学会・第32回日本臨床寄生虫学会合同大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 新規マラリアワクチン候補PfRiprに対するウサギモノクローナル抗体の評価2021

    • Author(s)
      徳永聡、長岡ひかる、小澤龍彦、岸裕幸、村口篤、坪井敬文、高島英造、澤崎達也
    • Organizer
      第90回日本寄生虫学会・第32回日本臨床寄生虫学会合同大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 熱帯熱マラリア原虫 MSP10の赤血球侵入におけるメカニズムの解明2020

    • Author(s)
      長岡ひかる、カノイ バーナード、神岡花奈、森田将之、ニリアン パラクパック、堀井俊宏、坪井敬文、高島英造
    • Organizer
      第89回日本寄生虫学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 熱帯熱マラリア発症阻止に関連する感染赤血球表面抗原のゲノム網羅的免疫スクリーニング2020

    • Author(s)
      高島英造、カノイ バーナード、長岡ひかる、パラックパック ニリアン、堀井俊宏、坪井敬文
    • Organizer
      第89回日本寄生虫学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 三日熱マラリアヒプノゾイト保有者の血清診断マーカーの開発と検証2020

    • Author(s)
      坪井敬文、高島英造、森田将之、 Longley Rhea、 White Michael、Harbes Matthias、 Ding Xavier、 Mueller Ivo
    • Organizer
      第89回日本寄生虫学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 愛媛発イノベーションによるマラリアワクチン開発への貢献2020

    • Author(s)
      坪井敬文
    • Organizer
      日本学術会議中国・四国地区会議主催学術講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 新規マラリアワクチン候補GAMAに対する侵入阻害抗体の作製2020

    • Author(s)
      曾我郁弥、徳永聡、小澤龍彦、長岡ひかる、高島英造、岸裕幸、村口篤、坪井敬文、 澤崎達也
    • Organizer
      第61回 日本生化学会中国・四国支部例会
    • Related Report
      2020 Annual Research Report
  • [Remarks] 愛媛大学プロテオサイエンスセンター・無細胞生命科学部門

    • URL

      https://www.pros.ehime-u.ac.jp/cell-free/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 愛媛大学プロテオサイエンスセンター・マラリア研究部門

    • URL

      https://www.pros.ehime-u.ac.jp/malaria/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 愛媛大学プロテオサイエンスセンター

    • URL

      http://www.pros.ehime-u.ac.jp

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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