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Research of Ca2+ signaling in Trypanosoma cruzi for drug discovery

Research Project

Project/Area Number 15K08452
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Parasitology (including sanitary zoology)
Research InstitutionNational Institute of Advanced Industrial Science and Technology (2016-2018)
Juntendo University (2015)

Principal Investigator

Muneaki Hashimoto  国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (30407308)

Research Collaborator Mikoshiba Katsuhiko  
Furukawa Koji  
Doi Motomichi  
Kurebayashi Nagomi  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsトリパノソーマ / Ca2+シグナリング / IP3受容体 / 阻害剤 / 細胞内Ca2+濃度 / 生体イメージング / 薬剤スクリーニング / カルシウムシグナリング / 分子基盤 / 創薬
Outline of Final Research Achievements

It is very important to develop drug for Chagas disease caused by Trypanosoma cruzi. In this study, research for drug development focusing on Ca2+ signaling mediated by a Ca2+ channel (TcIP3R), which regulates the parasite growth etc.. Importance of TcIP3R was investigated by electron microscopic analysis or live cell imaging. Furthermore, we developed novel antisense oligo nucleotides which inhibit TcIP3R expression in the parasites.

Academic Significance and Societal Importance of the Research Achievements

寄生原虫Trypanosoma cruziを病原体とするシャーガス病に対する現行の治療薬は、効果や副作用の点で実用的でなく、新規治療薬開発が急務である。本研究は、申請者らの独自研究を発展させ、T. cruziの分裂増殖・変態・細胞侵入などを制御するCa2+チャネル(TcIP3R)を介するCa2+シグナリングを標的とした治療薬開発のための基盤研究を行った。本成果により、トリパノソーマのCa2+シグナリングのユニークな点を顕在化したとともにその特異的阻害剤を新たに同定し、副作用のない治療薬開発で患者救済に貢献する。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2018 2017 2016 2015

All Journal Article (12 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 12 results,  Open Access: 9 results,  Acknowledgement Compliant: 3 results) Presentation (2 results) (of which Invited: 1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] PSEUDO iRBC BEADS AS POSITIVE CONTROL FOR CELL MICROARRAY CHIP-BASED DETECTION OF PLASMODIUM-INFECTED RBCs2018

    • Author(s)
      Hashimoto Muneaki、Numata Masahiko、Yatsushiro Shouki、Ido Yusuke、Tanaka Masato、Kajimoto Kazuaki、Kataoka Masatoshi
    • Journal Title

      Journal of Parasitology

      Volume: in press Issue: 3 Pages: 283-288

    • DOI

      10.1645/17-144

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hydrophilic-treated plastic plates for wide-range analysis of Giemsa-stained red blood cells and automated Plasmodium infection rate counting2017

    • Author(s)
      Hashimoto Muneaki、Yatsushiro Shouki、Yamamura Shohei、Tanaka Masato、Sakamoto Hirokazu、Ido Yusuke、Kajimoto Kazuaki、Bando Mika、Kido Jun-ichi、Kataoka Masatoshi
    • Journal Title

      Malaria Journal

      Volume: 16 Issue: 1 Pages: 321-321

    • DOI

      10.1186/s12936-017-1975-9

    • NAID

      120006767282

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sensitivity of Loop-Mediated Isothermal Amplification Increases 100-Fold after TritonTM?X-100 Treatment of?Plasmodium-Infected Erythrocytes2017

    • Author(s)
      Hashimoto Muneaki
    • Journal Title

      SOJ Microbiology & Infectious Diseases

      Volume: 5 Issue: 4 Pages: 1-2

    • DOI

      10.15226/sojmid/5/4/00177

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Haploinsufficiency of the folliculin gene leads to impaired functions of lung fibroblasts in patients with Birt-Hogg-Dubé syndrome.2016

    • Author(s)
      Hoshika Y, Takahashi F, Togo S, Hashimoto M, Nara T, Kobayashi T, Nurwidya F, Kataoka H, Kurihara M, Kobayashi E, Ebana H, Kikkawa M, Ando K, Nishino K, Hino O, Takahashi K, Seyama K
    • Journal Title

      Physiol Rep.

      Volume: 4

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inositol 1,4,5-trisphosphate receptor determines intracellular Ca2+ concentration in Trypanosoma cruzi throughout its life cycle2016

    • Author(s)
      Hashimoto M, Doi M, Kurebayashi N, Furukawa K, Hirawake-Mogi H, Ohmiya Y, Sakurai T, Mita T, Mikoshiba K, Nara T.
    • Journal Title

      FEBS Open Bio.

      Volume: 6(12) Issue: 12 Pages: 1178-1185

    • DOI

      10.1002/2211-5463.12126

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differential remodelling of peroxisome function underpins the environmental and metabolic adaptability of diplonemids and kinetoplastids.2016

    • Author(s)
      Morales J, Hashimoto M, Williams TA, Hirawake-Mogi H, Makiuchi T, Tsubouchi A, Kaga N, Taka H, Fujimura T, Koike M, Mita T, Bringaud F, Concepcion JL, Hashimoto T, Embley TM, Nara T.
    • Journal Title

      Proc R Soc B

      Volume: 283 Issue: 1830 Pages: 20160520-20160520

    • DOI

      10.1098/rspb.2016.0520

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Oct4 plays a crucial role in the maintenance of gefitinib-resistant lung cancer stem cells.2016

    • Author(s)
      Kobayashi I, Takahashi F, Nurwidya F, Nara T, Hashimoto M, Murakami A,
    • Journal Title

      Biochem Biophys Res Commun

      Volume: in press Issue: 1 Pages: 125-132

    • DOI

      10.1016/j.bbrc.2016.03.064

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Morpholino antisense oligo inhibits trans-splicing of pre-inositol 1,4,5-trisphosphate receptor mRNA of Trypanosoma cruzi and suppresses parasite growth and infectivity.2016

    • Author(s)
      Hashimoto M, Nara T, Mita T, Mikoshiba K.
    • Journal Title

      Parasitol Int.

      Volume: 65 Issue: 3 Pages: 175-179

    • DOI

      10.1016/j.parint.2015.12.001

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Plasmodium falciparum kelch 13: a potential molecular marker for tackling artemisinin-resistant malaria parasites.2016

    • Author(s)
      Mita T, Tachibana S, Hashimoto M, Hirai M.
    • Journal Title

      Expert Rev Anti Infect Ther.

      Volume: 14 Issue: 1 Pages: 125-135

    • DOI

      10.1586/14787210.2016.1106938

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bioinformatic identification of cytochrome b5 homologues from the parasitic nematode Ascaris suum and the free-living nematode Caenorhabditis elegans highlights the crucial role of A. suum adult-specific secretory cytochrome b5 in parasitic adaptation.2015

    • Author(s)
      Takamiya S, Hashimoto M, Mita T, Yokota T, Nakajima Y, Yamakura F, Sugio S,
    • Journal Title

      Parasitol Int.

      Volume: 65 Issue: 2 Pages: 113-20

    • DOI

      10.1016/j.parint.2015.11.004

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] A dominant negative form of inositol 1,4,5-trisphosphate receptor induces metacyclogenesis and increases mitochondrial density in Trypanosoma cruzi.2015

    • Author(s)
      Hashimoto M, Nara T, Enomoto M, Kurebayashi N, Yoshida M, Sakurai T, Mita T, Mikoshiba K.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 466 Issue: 3 Pages: 475-480

    • DOI

      10.1016/j.bbrc.2015.09.053

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Novel Method for Inducing Amastigote-To-Trypomastigote Transformation In Vitro in Trypanosoma cruzi Reveals the Importance of Inositol 1,4,5-Trisphosphate Receptor.2015

    • Author(s)
      Hashimoto M, Morales J, Uemura H, Mikoshiba K, Nara T.
    • Journal Title

      PLoS One.

      Volume: 10 Issue: 8 Pages: e0135726-e0135726

    • DOI

      10.1371/journal.pone.0135726

    • NAID

      120006986870

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Inositol 1,4,5-trisphosphate receptor determines intracellular Ca2+ concentration in Trypanosoma cruzi throughout its life cycle2016

    • Author(s)
      橋本宗明、戸井基道、呉林(国広)なごみ、古川功治、茂木(平訳)浩子、近江谷克裕、櫻井隆、美田敏宏、御子柴克彦、奈良武司
    • Organizer
      第85回日本寄生虫学会大会
    • Place of Presentation
      宮崎市民プラザ(宮崎県宮崎市)
    • Year and Date
      2016-03-19
    • Related Report
      2015 Research-status Report
  • [Presentation] トリパノソーマのCa2+シグナリング:IP3受容体の同定とその役割2015

    • Author(s)
      橋本宗明、呉林(国広)なごみ、戸井基道、榎本匡宏、モラレス ホルヘ、茂木(平訳)浩子、古川功治、上村春樹、吉田光孝、橋本哲男、櫻井隆、近江谷克裕、美田敏宏、御子柴克彦、奈良武司
    • Organizer
      第48回日本原生生物学会大会 今井壯一先生 メモリアルシンポジウム「寄生性原生生物学の最前線」
    • Place of Presentation
      国立感染症研究所 戸山庁舎(東京都新宿区)
    • Year and Date
      2015-11-07
    • Related Report
      2015 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] 米国特許庁2017

    • Inventor(s)
      橋本宗明、奈良武司、御子柴克彦
    • Industrial Property Rights Holder
      橋本宗明、奈良武司、御子柴克彦
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017-03-13
    • Related Report
      2016 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] 日本国特許庁2015

    • Inventor(s)
      御子柴克彦、奈良武司、橋本宗明
    • Industrial Property Rights Holder
      御子柴克彦、奈良武司、橋本宗明
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015
    • Acquisition Date
      2017
    • Related Report
      2017 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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