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

疟疾寄生虫的进化及其与宿主细胞的相互作用

• 批准号: 227689229
• 负责人: Professorin Dr. Iris Bruchhaus
• 金额: --
• 依托单位: Bernhard-Nocht-Institut für Tropenmedizin (BNITM)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/227689229?language=en
• 关键词: Evolution; Malaria; Parasites; their; Interactions

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.

疟疾是最常见和最具威胁性的传染病之一，每年有超过 5 亿病例，每年导致约 650,000 名受害者死亡。疟疾是由疟原虫属原生动物引起的，通过蚊子传播。这种危及生命的疾病几乎完全是由恶性疟原虫引起的，这种疾病仅限于热带气候。恶性疟原虫的特殊致病性涉及该物种特有的机制或可能遗传自共同的疟原虫祖先。在这个项目中，我们将整合系统发育、分子和细胞生物学方法来研究寄生虫与宿主细胞相互作用的进化。在这种情况下，我们将追溯 Laverania 亚属的起源，其中包括恶性疟原虫，来自假定的鸟类宿主。我们将阐明血孢子虫的系统发育，其中包括疟原虫和其他血液寄生虫。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宿主与寄生虫的相互作用。我们将专门评估疟原虫输出元件（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的恶性疟原虫中得到实验验证。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、MSP7）。最终，我们的项目将有助于揭示疟疾感染关键机制的演变。