Malaria intrahepatic interactions and trafficking: Deciphering the molecular machinery driving vesicular trafficking and membrane fusion between the hepatic host environment and malarial parasite for parasitophorous vacular membrane dynamics

疟原虫寄生虫在宿主肝脏中的细胞内发育和分化是疟疾疾病实际发作的先决条件。由于肝脏阶段在临床上是沉默的，并且可以通过消除免疫反应而完全消除，因此它们是迫切需要的创新抗疟药物和/或疫苗的有希望的目标。这些阶段发现于近60年前，与更容易接近的致病性红细胞阶段相比，关于它们的分子库和与它们的宿主细胞的相互作用仍然知之甚少。本项目的总体目标是拓宽肝内肝阶段寄生虫与宿主细胞室的基本动态细胞过程的知识。分化和复制的细胞内寄生虫居住在一个称为寄生虫空泡的膜隔室中，除了它自己的质膜外，还将其与宿主细胞质分开。在我们提出的研究过程中，我们的目标是集中在不同的蛋白质的特性，已知居住在寄生虫空泡室，并在同一时间破译潜在的成员的贩运网络和肝脏环境。这项研究的结果可以用于开发新的方法来预防疟疾疾病，此外还将提高我们对宿主/病原体相互作用的不同细胞生物学方面的理解。

The intracellular development and differentiation of the Plasmodium parasite in the host liver is a prerequisite for the actual onset of malaria disease. Since liver stages are clinically silent and can be completely eliminated by sterilising immune responses, they are promising targets for urgently needed innovative antimalarial drugs and/or vaccines. Discovered almost 60 years ago, these stages remain poorly understood regarding their molecular repertoire and interaction with their host cells in comparison to the better accessible pathogenic erythrocytic stages. The overall aim of this proposed project is to broaden the knowledge of fundamental dynamic cellular processes of the intrahepatic liver stage parasite with host cell compartments. The differentiating and replicative intracellular parasite resides in a membranous compartment called parasitophorous vacuole, separating it from the host cell cytoplasm in addition to its own plasma membrane. In the course of our proposed studies we aim at focussing on the characterisation of distinct proteins known to reside in the parasitophorous vacular compartment and at the same time deciphering potential members of the trafficking network from and to the hepatic environment. The results of this study can be exploited for the development of new approaches to prevent malaria disease and besides will improve our understanding of different cellbiological aspects of host/pathogen interactions.