| Project/Area Number |
18K15137
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49040:Parasitology-related
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| Research Institution | Ehime University |
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Principal Investigator |
BABA Minami 愛媛大学, プロテオサイエンスセンター, 研究員 (00814906)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | マラリア / スポロゾイト / 肝細胞 / ロプトリー分子 / RALP1 / sporozoite / liver stage / rhoptry / hepatocyte / RALP１ |
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| Outline of Final Research Achievements |
Rhoptry-associated leucine zipper-like protein 1 (RALP1) is one of rhoptry proteins which are conserved among in infective stage, merozoite and sporozoite. The attempts to generate RALP1 knockout parasites have failed possibly due to its essentiality for the parasite proliferation during blood stage. Therefore, until now, the function of RALP1 in sporozoites remains unelucidated.
To elucidate RALP1 function during sporozoite invasion, we applied the sporozoite stage-specific knockdown system by promoter swapping in the rodent malaria parasite strain, Plasmodium berghei. The amount of ralp1 mRNA in RALP1-cKD sporozoites were 10-fold lower than those in RALP1-control sporozoites. Parasitemias of RALP1-cKD sporozoite inoculated mice at 3 days after sporozoite inoculation were about 10-fold lower than those of RALP1-control sporozoite inoculated mice. It suggests that RALP1 plays an important role during liver infection stage of sporozoites.
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| Academic Significance and Societal Importance of the Research Achievements |
スポロゾイトが有しているロプトリーの分子の多くは、もう一つの感染型であるメロゾイトで必須であるために、ノックアウト原虫の作出ができず、逆遺伝学手法による機能解析が困難であった。本研究では、メロゾイトで必須であるRALP1を、プロモーター置換法を用いてスポロゾイト時期特異的に発現抑制することで、スポロゾイトの肝臓感染におけるRALP1の機能解析を可能にした。スポロゾイトに発現するロプトリー分子の機能を網羅的に解析することは、同様にロプトリーを有する他のアピコンプレクサ類に共通する、細胞寄生メカニズムの解明に繋がる。
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