| Project/Area Number |
17K08817
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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 Center for Global Health and Medicine |
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Principal Investigator |
Komaki-Yasuda Kana 国立研究開発法人国立国際医療研究センター, 研究所, 研究員 (50415551)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | マラリア原虫 / 転写因子 / RNA結合ドメイン / PREBP / 核局在 / ChIP-Seq / 表面抗原 / 細胞周期 / マラリア / 転写調節 / KHドメイン |
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| Outline of Final Research Achievements |
In this study, we observed cellular localization of the malaria parasite specific transcription factor PREBP, which has an RNA-binding domain characteristically, and Pf1, a protein of unknown function with a similar character. The difference in timing of nuclear localization of them was observed, suggesting their different working timing. Subsequently, candidate target genes of PREBP regulation were identified by ChIP-Seq analyses. Of the approximately 80 target gene candidates identified, approximately 40% were surface antigen proteins such as PfEMP1 and rifin. In the future, by clarifying how PREBP regulates the expression timing of these surface antigens, it can be expected that one part of the mechanism of parasitic adaptation in the host cell becomes clear.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、マラリア原虫の転写因子の活性の制御は転写因子自身の発現の有無では無く、核局在の調節によってなされていることを示唆され、これは原虫では全く新しい発見となった。このように転写因子の活性制御は赤血球内寄生期の細胞周期進行を支える根幹のメカニズムである可能性が示された。また、PREBPの新たなターゲット遺伝子候補としてPfEMP1に代表される表面抗原多型に関わる遺伝子を多数見出したことから、PREBPの作用がヒトの免疫から逃れようとするマラリア原虫の生存戦略の極めて重要な部分に関わっている可能性が示唆された。
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