Research of Ca2+ signaling in Trypanosoma cruzi for drug discovery
| Project/Area Number |
15K08452
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Parasitology (including sanitary zoology)
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| Research Institution | National Institute of Advanced Industrial Science and Technology (2016-2018)
Juntendo University (2015) |
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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)
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| Research Collaborator |
Mikoshiba Katsuhiko
Furukawa Koji
Doi Motomichi
Kurebayashi Nagomi
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(5 results)
Research Products
(16 results)
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[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
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Journal Title
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
FEBS Open Bio.
Volume: 6(12)
Issue: 12
Pages: 1178-1185
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Proc R Soc B
Volume: 283
Issue: 1830
Pages: 20160520-20160520
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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