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

疟疾寄生虫恶性疟原虫在其细胞内发育过程中向宿主细胞--成熟的人类红细胞--输出大量蛋白质。其中一些出口蛋白调节许多基本功能，包括细胞黏附和逃避宿主免疫系统，这与疾病的严重病理直接相关。然而，到目前为止，大多数出口蛋白质的功能仍然难以捉摸，因为大多数这些蛋白质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(Hsp40)家族的成员，该家族被输出到宿主细胞，并与更多寄生虫编码的输出蛋白的运输有关。这种蛋白质在宿主细胞中的确切功能仍然难以捉摸。该项目的目的是开发一种系统，使用先前确定的Hsp40作为模型蛋白质，能够对出口蛋白质进行功能分析。由于许多出口的蛋白质对寄生虫的生存是必不可少的，因此它们无法使用传统的基因失活和反向遗传策略。研究进一步出口的蛋白质的功能可能有助于确定对疟疾寄生虫的发病机制和生存至关重要的蛋白质。

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.