Genetic Analysis of Plasmodium falciparum Gametocyte Formation

描述(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，部分原因是抗击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，这种寄生虫在人类红细胞内繁殖。寄生虫的两种形式在人类血液中循环：无性分裂寄生虫(约95%)和配子体(男性和女性；约5%)。一旦被蚊子摄取，配子体就会发育成感染昆虫媒介的形式，而无性寄生虫则会死亡。疟原虫在人与人之间的传播严格取决于配子体的形成(配子体发生)。关于参与从疟原虫无性分化到有性期(配子体)的基因，我们知之甚少。我们计划通过转座子介导的插入突变和筛选不能形成配子体的突变来使用恶性疟原虫的全基因组遗传筛选，恶性疟原虫是人类最致命的寄生虫。这种方法是可行的，因为配子体的形成不是寄生虫在培养中生存所必需的(所需的突变体是活的)，并利用了转座子对受影响基因进行分子标记的事实，便于识别它。由于世界上近一半的人口面临感染疟疾的风险，迫切需要找到新的控制战略。对恶性疟原虫配子体发生的更好了解可能会导致防止配子体形成从而阻断传播的方法的发展。

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.