| Project/Area Number |
18K07095
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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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| Review Section |
Basic Section 49040:Parasitology-related
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| Research Institution | Juntendo University |
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Principal Investigator |
Hirai Makoto 順天堂大学, 医学部, 准教授 (50326849)
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | マラリア / ネズミマラリア原虫 / 薬剤耐性 / 適応度 / ミューテーター / 宿主特異性 / マラリア原虫 / 加速進化 / ミューテーターマラリア |
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| Outline of Final Research Achievements |
This study addressed this issue by utilizing a mutator strain of rodent malaria parasite.Initially, we attempted to identify the genetic factors that determine fitness in vertebrates (mice), particularly those under drug selection pressure. As a result, we identified novel mutations in drug resistance-conferring genes, and notably, successfully identified novel mutations in genes associated with resistance stabilization (resistance stabilization gene mutations). When drug resistance-conferring gene mutations were introduced into wild-type parasites, they exhibited weak resistance. However, upon further introduction of resistance stabilization gene mutations, resistance levels increased. Conversely, when only resistance stabilization gene mutations were introduced into wild-type parasites, no resistance was observed.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、マラリア原虫に薬剤耐性を付与する突然変異遺伝子変異を同定し、さらに耐性の安定化にかかわる新規遺伝子変異（耐性安定化遺伝子変異）の特定に成功した。本研究成果は、耐性安定化遺伝子変異が耐性付与遺伝子変異に作用することで、耐性の上昇と安定化にかかわるものと結論した。これらの結果は、現在問題となるマラリア薬剤耐性を解決するための重要な基礎データであり、耐性原虫の撲滅に寄与する大変重要な知見である。
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