Genetic Analysis of Plasmodium falciparum Gametocyte Formation

描述（由申请人提供）：疟疾是世界上最严重的传染病之一。病例数量正在增加，部分原因是对抗这种疾病的手段不足。疟疾是由原生动物寄生虫疟原虫引起的，疟原虫在人体红细胞内繁殖。两种形式的寄生虫在人类血液中循环：无性分裂的寄生虫（约95%）和配子细胞（雄性和雌性；约5%）。一旦被蚊子摄入，配子体发育成感染昆虫媒介的形式，而无性寄生虫则死亡。疟原虫从一个人传播到另一个人严格依赖于配子细胞的形成（配子细胞发生）。对于参与疟原虫从无性向有性阶段（配子体）分化的基因知之甚少。我们计划利用转座子介导的插入突变结合无法形成配子体的突变体，对人类寄生虫中最致命的恶性疟原虫进行全基因组遗传筛选。这种方法是可行的，因为寄生虫在培养中存活不需要配子体的形成（所需的突变体是可行的），并且利用了转座子分子标记受影响基因的事实，促进了其识别。由于世界上几乎一半的人口面临疟疾感染的风险，必须找到新的控制战略。对恶性疟原虫配子细胞形成的更好理解可能会导致阻止配子细胞形成的方法的发展，从而阻断传播。

DESCRIPTION (provided by applicant): Malaria is one of the most serious infectious diseases in the world. The number of cases is increasing, in part because of insufficient means to fight the disease. Malaria is caused by the protozoan parasite Plasmodium, which multiplies within human red blood cells. Two forms of the parasite circulate in the human blood: asexually dividing parasites (approximately 95%) and gametocytes (male and female; approximately 5%). Once ingested by the mosquito, the gametocytes develop into forms that infect the insect vector while the asexual parasites die. Transmission of Plasmodium from one person to the next strictly depends on formation of gametocytes (gametocytogenesis). Little is known about genes that are involved in the differentiation from the Plasmodium asexual to the sexual stages (gametocyte). We plan to use a genome-wide genetic screen of P. falciparum, the deadliest of the human parasites, by use of transposon-mediated insertional mutagenesis combined with a screen for mutants incapable to form gametocytes. This approach is feasible because gametocyte formation is not required for parasite survival in culture (the desired mutants are viable) and takes advantage of the fact that transposons molecularly mark the affected gene, facilitating its identification. With almost half of the world's population at risk of malaria infection, it is imperative to find new control strategies. A better understanding of P. falciparum gametocytogenesis may lead to the development of means to prevent gametocyte formation and thus, block transmission.