| Project/Area Number |
16H05182
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Parasitology (including sanitary zoology)
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| Research Institution | Ehime University |
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Principal Investigator |
Ishino Tomoko 愛媛大学, プロテオサイエンスセンター, 准教授 (40402680)
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| Co-Investigator(Kenkyū-buntansha) |
橘 真由美 愛媛大学, プロテオサイエンスセンター, 助教 (00301325)
鳥居 本美 愛媛大学, プロテオサイエンスセンター, 教授 (20164072)
馬場 みなみ 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) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | マラリア / スポロゾイト / 肝臓感染 / 肝細胞侵入 / 肝細胞寄生 / 肝細胞規制 / RON3 |
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| Outline of Final Research Achievements |
Malaria transmission to humans initiates by sporozoite infection of hepatocytes, which are inoculated by infected Anopheles mosquitoes. To develop the infection inhibitory vaccines, the step of sporozoite invasion of hepatocytes is one of the ideal targets, however its molecular mechanisms are not elucidated clearly. The aim of this study is to elucidate the molecular mechanisms of sporozoite invasion by focusing on RON3, the secretory protein stored in rhoptries in both merozoites and sporozoites. By generating sporozoite stage-specific RON3 conditional knockdown parasites in Plasmodium berghei, RON3 functions during sporozoite invasion was investigated in vitro and in vivo. Moreover, specific antibodies against partial recombinant RON3 were raised in rabbits to examine their inhibitory effects on sporozoite infection.
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| Academic Significance and Societal Importance of the Research Achievements |
私たちが開発したスポロゾイト時期特異的遺伝子発現抑制法を適応することで、寄生型（メロゾイト、スポロゾイト）に共通に発現する分子の機能解析が可能になった。この方法により、これまで感染に関わることが示唆されていた複数の分泌型タンパク質の機能解析が行える様になり、RON2, RON11がスポロゾイトの接着や運動能に関わることで細胞侵入に関与することを、RON3は哺乳類肝臓感染に関わることを明らかにした。今後の感染阻止ワクチン開発に向けての論理的基盤を与えるものとなる。
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