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Molecular interactions of the malaria parasite sexual stages during fertilization in the mosquito midgut
With a death toll of 1 - 3 million per year malaria is one of the major infectious diseases. Of the four human specific malaria agents, Plasmodium falciparum is the most harmful species. The parasites sexual phase, which starts with the formation of gametocytes, is an important part of the parasite's life cycle, since it is crucial for the transmission of the disease. After their uptake during the blood meal of the mosquito, the gametocyte sexual stages become activated, triggered by the mosquito-derived molecule xanthurenic acid and a drop in temperature. The activated gametocytes develop into gametes which egress from the enveloping erythrocyte. Upon fertilization a zygote is formed, which subsequently transforms into a motile ookinete. By disrupting the epithelium the ookinete leaves the midgut lumen. Gametes, zygotes and ookinetes are considered bottleneck stages with an approximate 300-fold decrease of parasite number from gametocytes to ookinetes. These extracellular stages of the malaria parasite simultaneously have to cope with the hostile environment of the mosquito midgut and perceive signals of the invertebrate vector. |
 Andrea Kühn, Würzburg |
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In the course of my PhD thesis I am investigating molecular interactions of proteins which are specifically expressed in the sexual stages of P. falciparum. This study aims at characterizing interactions between gametocytes and gametes respectively, as well as interactions of parasite proteins with molecules of the mosquito midgut. The object of an additional project is to gain insight in the signal transduction pathway leading to gametocyte activation by identifying the receptor of xanthurenic acid. |
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