Genetic Analysis of Plasmodium falciparum Gametocyte Formation

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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.