Protein trafficking in malaria parasite-infected erythrocytes

疟疾每年导致100万至300万儿童死亡。此外，这种疾病使疟疾流行地区的成年人口衰弱，从而加剧了许多第三世界国家的贫穷循环。随着对现有抗疟药物的耐药性增加，迫切需要在分子水平上了解寄生虫的工作原理，以便制定替代的抗疟策略。在其生命周期的一部分，疟疾寄生虫感染其人类宿主的红细胞。寄生虫将蛋白质运输到红细胞膜，以改变其所采用的细胞住所的性质。沉积在红细胞膜上或细胞膜内的寄生虫蛋白增加了被寄生红细胞的渗透性和粘性。这样可以更有效地吸收营养，并使寄生红细胞粘附在血管壁上，从而避免通过脾脏。被寄生的红细胞粘附在脑中的毛细血管上被认为会导致被称为脑疟疾的并发症的发展。这一并发症是造成大多数疟疾死亡的原因。为了将黏附蛋白运输到红细胞表面，寄生虫建立了新的运输途径，在红细胞细胞质中移动蛋白质。由于未感染的红细胞没有办法也不需要移动蛋白质，这种新的运输机制可能代表了杀死疟疾寄生虫而对人类无毒的药物的靶标。受感染红细胞周围蛋白质运动的途径在很大程度上是未知的。我们建议使用细胞生物学技术和技术将外源基因引入疟疾感染的红细胞，以揭示寄生虫用于将蛋白质运送到其接受的家园的正确目的地的分子机制和票票系统的细节。

Malaria kills between 1 and 3 million children each year. In addition, the disease debilitates the adult population in malaria-endemic areas, thereby contributing to the cycle of poverty in many third world countries. As resistance to existing antimalarial drugs increases, there is an urgent need to understand the workings of the parasite at a molecular level to enable the development of alternative antimalarial strategies. During part of its life cycle, the malaria parasite infects the erythrocytes of its human host. The parasite transports proteins to the erythrocyte membrane so as to modify the properties of its adopted cellular residence. The parasite proteins that are deposited at or in the erythrocyte membrane increase the leakiness and the stickiness of the parasitised erythrocytes. This allows more efficient uptake of nutrients and allows the parasitised erythrocytes to adhere to blood vessel walls, thereby avoiding passage through the spleen. Adherence of parasitised erythrocytes to capillaries in the brain is thought to lead to the development of the complication known as cerebral malaria. This complication is responsible for most of the deaths due to malaria. In order to traffic the adherence proteins to the erythrocyte surface, the parasite establishes novel transport pathways for moving proteins across the erythrocyte cytoplasm. As the uninfected erythrocyte has no means, nor requirement, for moving proteins, this novel transport mechanism may represent a target for drugs that kill the malaria parasite without being toxic to humans. The pathways for the movement of proteins around the infected erythrocyte are largely unknown. We propose to use cell biology techniques and techniques to introduce foreign genes into malaria-infected erythrocytes to unravel the details of the molecular machinery and the ticketing system that the parasite uses to traffic proteins to their correct destinations in its adopted home.