Molecular dissection of the nuclear division according to the developmental stages in Plasmodium

• Project/Area Number: 18K07097
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49040:Parasitology-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Annoura Takeshi 国立感染症研究所, 寄生動物部, 主任研究官 (90407239)
• Co-Investigator(Kenkyū-buntansha): 佐々木 年則 国立感染症研究所, 昆虫医科学部, 主任研究官 (10300930) ; 川合 覚 獨協医科大学, 医学部, 教授 (70275733)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: マラリア / 核の制御 / 休眠 / 増殖 / 電子顕微鏡 / 増殖分子メカニズム / 休眠期 / 核

Outline of Final Research Achievements

Plasmodium is a unicellular eukaryotic parasite that is the causative agent of malaria, which is transmitted by Anopheles mosquito. The Plasmodium liver-stage parasite represents the first intracellular infectious step in human following a mosquito bite, and this asymptomatic stage forms several thousands of merozoites with tremendous multinuclear hyper-proliferation. Some Plasmodium species generate a dormant uninucleate parasite during liver-stage development termed the hypnozoite which persists for months or even years following an infection. The developmental decision-making that controls dormancy (or promote proliferation) in Plasmodium liver-stage is made before nuclear segregation. However, the detailed molecular mechanism(s) that regulates proliferation is poorly understood. In this study, we used focused-ion-beam-milling combined with scanning-electron-microscopy to revel the 3D architecture during nuclear segregation in several developmental stages in Plasmodium.

Academic Significance and Societal Importance of the Research Achievements

マラリアは、結核・エイズなどと共に世界中に蔓延する感染症の一つであり、赤道付近の熱帯・亜熱帯地域などを中心に広く流行し、様々な対策がなされているが制圧には至っていない。マラリアの病原体であるマラリア原虫はハマダラカによって媒介され、ヒト体内において肝細胞内（肝内型）と赤血球内（赤内型）に寄生する疾患であり、肝内型原虫は休眠期を有しており根治が難しくマラリア対策を困難にする。本研究では、この肝内型原虫の増殖・休眠の分子制御を明らかにするため、核の制御に着目し分子細胞生物学、逆遺伝学、電子顕微鏡学などのアプローチにより分子基盤の解明を試みることで、新たなマラリア対策に付与する研究を展開した。