Trafficking of the cytoadherence-mediating protein to the host cell surface in malaria parasite-infected erythrocytes

疟疾每年导致100万至300万儿童死亡。此外，这种疾病削弱了疟疾流行地区的成年人口，从而助长了许多第三世界国家的贫困循环。随着对现有抗疟疾药物耐药性的增加，迫切需要在分子水平上了解寄生虫的工作原理，以便能够开发替代的抗疟疾策略。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上，从而改变其所采用的细胞居住地的性质。沉积在红细胞膜或红细胞膜中的寄生虫蛋白增加了寄生红血球的泄漏性和粘性。这可以更有效地吸收营养物质，并使寄生的红细胞附着在血管壁上，从而避免通过脾。被寄生的红血球附着在大脑和胎盘的毛细血管上，被认为会导致所谓的“脑型”和“胎盘型”疟疾的发展。这些并发症导致许多儿童和孕妇死亡。我们建议使用细胞生物学技术将外来基因引入疟疾寄生虫感染的红细胞中，以揭示疟疾寄生虫用来将其毒力蛋白运送到正确目的地的分子机制和票务系统的细节。这些研究可能会导致新的干预策略的开发。例如，如果有可能降低一种名为PfEMP1的蛋白质的表面表达水平，那么感染的红细胞的粘附性就会受到抑制。这将大大降低这种重要的人类病原体的影响。

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 red blood cells of its human host. The parasite transports proteins to the red blood cell membrane so as to modify the properties of its adopted cellular residence. The parasite proteins that are deposited at or in the red blood cell membrane increase the leakiness and the stickiness of the parasitised red blood cells. This allows more efficient uptake of nutrients and allows the parasitised red blood cells to adhere to blood vessel walls, thereby avoiding passage through the spleen. Adherence of parasitised red blood cells to capillaries in the brain and the placenta is thought to lead to the development of the complications known as 'cerebral' and 'placental' malaria. These complications are responsible for the deaths of many children and pregnant women. We propose to use cell biology techniques to introduce foreign genes into malaria parasite-infected red blood cells to unravel the details of the molecular machinery and the ticketing system that the parasite uses to traffic its virulence proteins to their correct destinations. These studies could potentially lead to the development of novel intervention strategies. For example, if it were possible to decrease the levels of surface expression of a protein known as PfEMP1, adhesion of infected red blood cells would be inhibited. This would greatly decrease the impact of this important human pathogen.