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

疟疾寄生虫在血餐期间从人类宿主传播到蚊子媒介后开始有性繁殖。性阶段是寄生虫的唯一生命周期阶段，能够在蚊子中建立感染，从而在热带疾病的传播中发挥重要作用。性前体细胞，即配子体，从包膜的宿主红细胞中流出，是由蚊子中肠的刺激触发的，涉及红细胞膜和寄生虫液泡膜两种膜的破裂。配子体出口对于配子的形成是至关重要的，但其潜在的分子机制至今还不清楚。本研究的目的是在超微结构水平上解剖人类疟疾寄生虫恶性疟原虫的配子体从红细胞流出的不同步骤。我们的重点将集中在研究蛋白酶和磷脂酶在膜解体中的功能，以及确定寄生虫来源的穿孔素在寄生虫液泡膜破裂中的潜在作用。技术包括抑制试验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.