Functional analysis of exported Plasmodium falciparum proteins by specific conditional regulation of protein transport

恶性疟原虫在其细胞内发育期间向宿主细胞（成熟的人红细胞）输出大量蛋白质。这些输出的蛋白质中的一些介导许多基本功能，包括宿主免疫系统的细胞粘附和逃避，这与疾病的严重病理学直接相关。然而，迄今为止，大多数输出蛋白的功能仍然难以捉摸，因为这些蛋白中的大多数缺乏任何已知的结构域结构。在最近的一项研究中，我们已经确定了热休克蛋白40（HSP 40）家族的成员，该家族被输出到宿主细胞，并参与进一步的寄生虫编码的输出蛋白的运输。这种蛋白质在宿主细胞内的确切功能仍然难以捉摸。该项目的目的是开发一个系统，使出口蛋白质的功能分析，使用以前确定的HSP 40作为模型蛋白质。由于许多输出蛋白是寄生虫生存所必需的，因此它们不能被传统的基因失活和逆转遗传策略所获得。研究进一步输出的蛋白质的功能可能允许分配对疟原虫的发病机制和存活很重要的蛋白质。

During its intracellular development the malaria parasite Plasmodium falciparum exports a large number of proteins to the host cell, mature human erythrocytes. Some of these exported proteins mediate numerous essential functions including cytoadherence and evasion of the hosts immune system, that are directly linked to the severe pathology of the disease. However, the function of most exported proteins remains, to date, elusive as most of these proteins lack any known domain structures. In a recent study, we have identified members of the heat shock protein 40 (HSP40) family that is exported to the host cell, and implicated in transport of further parasite-encoded exported proteins. The exact function of this protein within the host cell remains elusive. The aim of this project is the development of a system to enable the functional analysis of exported proteins, using the previously identified HSP40 as a model protein. As many exported proteins are essential for the parasites survival, they are therefore not accessible to traditional gene inactivation and reverse genetic strategies. Studying the function of further exported proteins may allow the assignment of proteins that are important for pathogenesis and survival of the malaria parasite.