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

宿主肝脏内疟原虫的细胞内发育和分化是疟疾实际发病的先决条件。由于肝脏阶段在临床上是沉默的，并且可以通过对免疫反应进行消毒来完全消除，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。发现于近60年前，与更容易获得的病原性红细胞阶段相比，这些阶段对其分子库和与宿主细胞的相互作用仍然知之甚少。本项目的总体目标是扩大对具有宿主细胞室的肝内肝期寄生虫基本动态细胞过程的认识。分化和复制的细胞内寄生虫居住在一个被称为寄生液泡的膜室中，将其与宿主细胞质以及自身的质膜分开。在我们提出的研究过程中，我们的目标是集中在已知的寄生空室中存在的不同蛋白质的特征上，同时破译来自和进入肝脏环境的运输网络的潜在成员。这项研究的结果可以用于开发预防疟疾的新方法，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.