The Evolution of Malaria Parasites and their Interactions with their Host Cell

疟疾是最常见和最具威胁性的传染病之一，每年有超过5亿例病例，每年约有65万人死亡。疟疾是由疟原虫属的原生动物引起的，由蚊子传播。这种危及生命的疾病几乎完全由恶性疟原虫引起，仅限于热带气候。恶性疟原虫的特殊致病性涉及该物种特有的机制或可能从共同的疟原虫祖先遗传的机制。在这个项目中，我们将整合系统发育，分子和细胞生物学的方法来研究寄生虫-宿主细胞相互作用的进化。在这种情况下，我们将跟踪亚属Laverania，其中包括恶性疟原虫，从一个puerecavian主机的起源。我们将阐明血孢子虫，其中包括疟原虫和其他血液寄生虫的生殖。宿主-寄生虫相互作用将通过研究从红细胞内疟原虫到宿主细胞表面的蛋白质输出来解决。我们将专门评估疟原虫输出元素（PEXEL）的灵活性。结果将用于更好地预测疟原虫物种的输出组，这将在转基因寄生虫中对恶性疟原虫进行实验验证。此外，我们将特别关注介导寄生虫-宿主细胞相互作用的选定蛋白质家族（PIR，MSP 7）。最后，我们的项目将有助于揭示疟疾感染的关键机制的演变。

Malaria is one of the most common and threatening infectious diseases with more than 500 million annual cases, fatal for ~650,000 victims per year. Malaria is caused by protozoans of the genus Plasmodium, which are transmitted by mosquitoes. The life-threatening forms of the disease are almost exclusively caused by P. falciparum, which is limited to tropical climates. The particular pathogenicity of P. falciparum involves mechanisms that are either specific for this species or that may be inherited from a common Plasmodium ancestor. In this project, we will integrate phylogenetic, molecular and cell biology approaches to study the evolution of parasite-host cell interactions. In this context, we will trace the origin of the subgenus Laverania, which include P. falciparum, from a putatively avian host. We will elucidate the phylogeny of the Haemosporida, which include Plasmodium and other blood-parasites. Host-parasite interactions will be tackled by studying the protein export from the intraerythrocytic Plasmodium to the host cell surface. We will specifically evaluate the flexibility of the Plasmodium export element (PEXEL). The results will be used to better predict the exportomes of the Plasmodium species, which will be experimentally verified for P. falciparum in transgenic parasites. In addition, we will specifically focus on selected protein families that mediate parasite-host cell interactions (PIR, MSP7). To the end, our project will help unravelling the evolution of crucial mechanisms of malaria infections.