Insights into the molecular machinery involved in regulating Plasmodium liver-stage proliferation

• Project/Area Number: 15K08455
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Annoura Takeshi 国立感染症研究所, 寄生動物部, 主任研究官 (90407239)
• Co-Investigator(Kenkyū-buntansha): 佐々木 年則 国立感染症研究所, 昆虫医科学部, 主任研究官 (10300930)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: マラリア / 肝内型原虫 / 増殖分子メカニズム / 寄生胞膜 / 高速増殖 / 核の増殖制御

Outline of Final Research Achievements

The protozoan parasites Plasmodium is the etiological agents of malaria that is transmitted by the Anopheles mosquito to human. The Plasmodium liver-stage parasite represents the first of the intracellular infectious step in human following a mosquito bite, and this asymptomatic stage forms many thousands of merozoites with have undergone tremendous multinuclear hyper-proliferation. Some Plasmodium species generate a dormant uninucleate parasite during liver-stage development termed the hypnozoite which persists for months or even years following an infection. The developmental decision-making that controls promotes proliferation (or dormancy) in Plasmodium liver-stage is made before nuclear segregation. However, the detailed molecular mechanism(s) that regulates proliferation is poorly understood. We employed the rodent malaria models P. berghei to reveal molecular insights into Plasmodium liver-stage development.

Research Products

• [Journal Article] Cutaneous leishmaniasis caused by Leishmania tropica in Israel. (2018)
  • Author(s): Uchida S, Oiso N, Sanjoba C, Matsumoto Y, Yanagihara S, Annoura T, Kato Y, Shirano M, Goto Y, Kawada A.
  • Journal Title: J Dermatol Volume: 印刷中 Issue: 9
  • DOI: 10.1111/1346-8138.14300
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] LC3-association with the parasitophorous vacuole membrane of Plasmodium berghei liver stages follows a noncanonical autophagy pathway. (2017)
  • Author(s): 2.Wacker R, Eickel N, Schmuckli-Maurer J, Annoura T, Niklaus L, Khan SM, Guan JL, Heussler VT.
  • Journal Title: Cell Microbiol. Volume: in press Issue: 10 Pages: e12754-e12754
  • DOI: 10.1111/cmi.12754
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Characterization and diagnostic application of Trypanosoma cruzi trypomastigote excreted-secreted antigens shed in exosomes released from infected mammalian cells. (2017)
  • Author(s): Bautista-Lopez N, Ndao M, Camargo F, Nara T, Jardim A, Annoura T, Hardie D, Borchers C.
  • Journal Title: J Clin Microbiol. 2017 55:744-758. Volume: 55 Issue: 3 Pages: 744-758
  • DOI: 10.1128/jcm.01649-16
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Variant exported blood-stage proteins encoded by Plasmodium multigene families are expressed in liver stages where they are exported into the parasitophorous vacuole. (2016)
  • Author(s): Fougere A, Jackson AP, Bechtsi DP, Braks JA, Annoura T, Fonager J, Spaccapelo R, Ramesar J, Chevalley-Maurel S, Klop O, van der Laan AM, Tanke HJ, Kocken CH, Pasini EM, Khan SM, Bohme U, van Ooij C, Otto TD, Janse CJ, Franke-Fayard BM.
  • Journal Title: PLoS Pathog. Volume: 12(11) Issue: 11 Pages: e1005917-e1005917
  • DOI: 10.1371/journal.ppat.1005917
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Vital and dispensable roles of Plasmodium multidrug resistance transporters during blood- and mosquito-stage development. (2016)
  • Author(s): 1.Rijpma SR, van der Velden M, Annoura T, Matz JM, Kenthirapalan S, Kooij TW, Matuschewski K, van Gemert GJ, van de Vegte-Bolmer M, Siebelink-Stoter R, Graumans W, Ramesar J, Klop O, Russel FG, Sauerwein RW, Janse CJ, Franke-Fayard BM, Koenderink JB..
  • Journal Title: Mol Microbiol. Volume: In press Issue: 1 Pages: 78-91
  • DOI: 10.1111/mmi.13373
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Multidrug ABC transporters are essential for hepatic development of Plasmodium sporozoites. (2016)
  • Author(s): Rijpma SR, van der Velden M, González-Pons M, Annoura T, van Schaijk BC, van Gemert GJ, van den Heuvel JJ, Ramesar J, Chevalley-Maurel S, Ploemen IH, Khan SM, Franetich JF, Mazier D, de Wilt JH, Serrano AE, Russel FG, Janse CJ, Sauerwein RW, Koenderink JB, Franke-Fayard BM.
  • Journal Title: Cell Microbiol. Volume: 18 Issue: 3 Pages: 369-83
  • DOI: 10.1111/cmi.12517
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 肝内型マラリア原虫の休眠分子メカニズムの解明 (2018)
  • Author(s): 案浦 健、 荒木 球沙、川合 覚、小林 宏尚、片岡 紀代、角田 宗一郎、Wacker R、Janse CJ、 Khan SM、 Heussler VT、野崎 智義、久枝 一
  • Organizer: 第87回 日本寄生虫学会大会
• [Presentation] 肝内型マラリア原虫の休眠・増殖分子メカニズムの解明 (2017)
  • Author(s): 案浦 健, 荒木 球沙, Franke-Fayard BM, Janse CJ, 川合 覚, Khan SM, Heussler VT, 野崎 智義
  • Organizer: 第90回 日本細菌学会
  • Place of Presentation: 仙台国際センター展示棟
  • Year and Date: 2017-03-19
  • Invited
• [Presentation] 肝内型マラリア原虫の休眠・増殖分子メカニズムの解明 (2017)
  • Author(s): 案浦 健、 荒木 球沙、川合 覚、小林 宏尚、片岡 紀代、Wacker R、Janse CJ、 Khan SM、 Heussler VT、野崎 智義
  • 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合同大会
• [Presentation] 肝内型マラリア原虫の休眠・増殖分子メカニズムの解明 (2017)
  • Author(s): 案浦 健、 荒木 球沙、川合 覚、小林 宏尚、片岡 紀代、Wacker R、Janse CJ、 Khan SM、 Heussler VT、野崎 智義
  • Organizer: 第50回日本原生生物学会大会・第1回日本共生生物学会大会 合同大会
  • Invited
• [Presentation] 肝内型マラリア原虫の休眠・増殖分子メカニズムの解明 (2017)
  • Author(s): 案浦 健、 荒木 球沙、川合 覚、Wacker R、Janse CJ、 Khan SM、 Heussler VT、野崎 智義
  • Organizer: 2017年度生命科学系学会合同年次大会 ConBio2017
  • Invited
• [Presentation] マラリア原虫弱毒生ワクチン開発の現状と展望 (2017)
  • Author(s): 案浦 健
  • Organizer: バイオロジクスフォーラム 第14回 学術集会
  • Place of Presentation: 文京シビックホール
  • Invited
• [Presentation] 肝内型マラリア原虫- 宿主間“ 鬩ぎ合い” 分子メカニズムの解明 (2016)
  • Author(s): 案浦 健, 荒木 球沙, Franke-Fayard BM, Janse CJ, 川合 覚, Khan SM, Heussler VT, 野崎 智義
  • Organizer: 第57回日本熱帯医学会大会
  • Place of Presentation: 一橋大学 一橋講堂（東京都千代田区一ツ橋）
  • Year and Date: 2016-11-05
  • Invited
• [Presentation] 肝内型マラリア原虫の増殖分子メカニズムの解明 (2016)
  • Author(s): 案浦 健, 荒木 球沙, Franke-Fayard BM, Janse CJ, 川合 覚, Khan SM, Heussler VT, 野崎 智義
  • 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合同大会
  • Place of Presentation: 帯広畜産大学・原虫病研究センター PKホール
  • Year and Date: 2016-08-21
• [Presentation] 肝内型マラリア原虫の休眠・増殖分子メカニズムの解明 (2016)
  • Author(s): 案浦 健, 荒木 球沙, Franke-Fayard BM, Janse CJ, 川合 覚, Khan SM, Heussler VT, 野崎 智義
  • Organizer: 第12回 霊長類医科学フォーラム
  • Place of Presentation: つくば市の文部科学省研究交流センター
  • Invited
• [Presentation] 肝内型マラリア原虫-宿主間“鬩ぎ合い”分子メカニズムの解明 (2015)
  • Author(s): 案浦 健, 荒木 球沙, Franke-Fayard BM, Janse CJ, 浅井 史敏, Khan SM, Heussler VT, 野崎 智義
  • Organizer: BMB2015（第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会）
  • Place of Presentation: 神戸ポートピアホテル、他
  • Year and Date: 2015-11-30
• [Presentation] 細胞内・寄生原虫による“宿主ハイジャック生物学 ”の解明 (2015)
  • Author(s): 案浦 健, 荒木 球沙, Franke-Fayard BM, Janse CJ, 浅井 史敏, 川合 覚, Khan SM, Heussler VT, 野崎 智義
  • Organizer: 第9回細菌学若手コロッセウム
  • Place of Presentation: KKR ホテル敬天閣
  • Year and Date: 2015-11-23
• [Presentation] New member of the Plasmodium 6-Cys family B9 have distinct and critical roles in liver stage development (2015)
  • Author(s): Annoura T, van Schaijk BC, Ploemen IH, Sajid M, Lin JW, Vos MW, Dinmohamed AG, Inaoka DK, Rijpma SR, van Gemert GJ, Chevalley-Maurel S, Kiełbasa SM, Scheltinga F, Franke-Fayard B, Klop O, Hermsen CC, Kita K, Gego A, Franetich JF, Mazier D, Nozaki T, Hoffman SL, Janse CJ, Sauerwein RW, Khan SM.
  • Organizer: 2nd International Symposium Matryoshka-type Evolution of Eukaryotic Cells
  • Place of Presentation: 筑波大学 大学会館
  • Year and Date: 2015-10-01
  • Int'l Joint Research
• [Presentation] 肝内型マラリア原虫と宿主の“鬩ぎ合い”生物学の解明にむけて・・・ (2015)
  • Author(s): 案浦 健, 荒木 球沙, Franke-Fayard BM, Janse CJ, 浅井 史敏, 川合 覚, Khan SM, Heussler VT, 野崎 智義
  • Organizer: 第２３回分子寄生虫学ワークショップ／第１３回分子寄生虫・マラリア研究フォーラム合同大会
  • Place of Presentation: 帯広畜産大学・原虫病研究センター PKホール
  • Year and Date: 2015-08-30
• [Presentation] New members of the Plasmodium 6-Cys family-related proteins have distinct and critical roles in liver stage development (2015)
  • Author(s): Annoura T, van Schaijk BC, Ploemen IH, Sajid M, Lin JW, Vos MW, Dinmohamed AG, Inaoka DK, Rijpma SR, van Gemert GJ, Chevalley-Maurel S, Kiełbasa SM, Scheltinga F, Franke-Fayard B, Klop O, Hermsen CC, Kita K, Gego A, Franetich JF, Mazier D, Nozaki T, Hoffman SL, Janse CJ, Sauerwein RW, Khan SM.
  • Organizer: 26th Annual Molecular Parasitology/Vector Biology Symposium
  • Place of Presentation: アメリカ・ジョージア州・アセンズ（ジョージア大学）
  • Year and Date: 2015-04-28
  • Int'l Joint Research
• [Book] 有害微生物の制御と管理 (2016)
  • Author(s): 案浦健
  • Total Pages: 629
  • Publisher: テクノシステム