The egress of malaria gametocytes from the red blood cell following parasite transmission to the mosquito

疟疾寄生虫的有性繁殖是在吸血期间从人类宿主传播到蚊子载体之后开始的。性阶段是寄生虫生命周期中唯一能够在蚊子中建立感染的阶段，因此对热带疾病的传播起着重要作用。性前体细胞（配子母细胞）从被包围的宿主红细胞中的流出是由蚊子中肠的刺激触发的，并且涉及两个膜的破裂，红细胞膜和寄生虫空泡的膜。配子体排出对于配子的形成至关重要，但其潜在的分子机制至今尚未得到很好的理解。这是本建议的目的解剖的超微结构水平上的配子体从红细胞在人类疟疾寄生虫恶性疟原虫出口的不同步骤。我们的特别重点将在于调查蛋白酶和磷脂酶在膜崩解的功能，并确定寄生虫衍生的穿孔素在寄生虫空泡膜破裂的潜在作用。技术包括抑制剂测定以及反向遗传学和显性负表达方法结合共聚焦激光扫描和电子显微镜。

Sexual reproduction of the malaria parasite is initiated following its transmission from the human host to the mosquito vector during a blood meal. The sexual stages are the only life-cycle stages of the parasite that are able to establish an infection in the mosquito and thus play an important role for spread of the tropical disease. The egress of sexual precursor cells, the gametocytes, from the enveloping host erythrocyte is triggered by stimuli of the mosquito midgut and involves the rupture of two membranes, the erythrocyte membrane and the membrane of the parasitophorous vacuole. Gametocyte egress is crucial for the formation of gametes, but the underlying molecular mechanisms are up to date not well understood. It is the aim of this proposal to dissect on the ultrastructural level the distinct steps of gametocyte egress from the erythrocyte in the human malaria parasite Plasmodium falciparum. Our particular focus will lie on investigating the functions of proteases and phopholipases in membrane disintegration and on determining the potential role of parasite-derived perforins in the rupture of the parasitophorous vacuole membrane. Techniques include inhibitor assays as well as reverse genetics and dominant negative expression approaches in combination with confocal laser scanning and electron microscopy.