The Plasmodial Surface Anion Channel And Malaria Parasit

顶复合体分子生理学单位对感染疟疾寄生虫的人红细胞的各种膜上离子和营养物质的运输进行基础研究。这项工作结合了分子生物学和信息学、蛋白质和脂质生物化学、各种运输测定、生物物理学和化合物文库的高通量筛选。我们最近使用电生理学方法鉴定了感染恶性疟原虫的人红细胞上的一个不寻常的离子通道，恶性疟原虫是导致最致命形式的疟疾的原因。这种通道，即疟原虫表面阴离子通道（plasmodial surface阴离子通道，PSAC），存在于1000个拷贝/细胞中，具有不同寻常的门控特性，并且可以渗透到寄生虫生长所需的一系列阴离子和营养物质中。我们提出PSAC介导了一个循序渐进的营养获取扩散途径的第一步。实验室目前的项目包括：1)表征PSAC的渗透机制；2)开发和测试可能作为未来抗疟药物的特异性PSAC阻断剂；3)克隆PSAC和其他转运蛋白的编码基因；4)这些转运蛋白的异源表达。这些项目旨在了解寄生虫的生理学，并制定控制疟疾的新策略。

The Apicomplexan Molecular Physiology Unit conducts basic research on the transport of ions and nutrients across various membranes of human red blood cells infected with malaria parasites. This work incorporates molecular biology and informatics, protein and lipid biochemistry, various transport assays, biophysics, and high-throughput screening of compound libraries. We recently used electrophysiological methods to identify an unusual ion channel on human red blood cells infected with P. falciparum, which causes the deadliest form of malaria. This channel, the plasmodial surface anion channel (PSAC), is present at 1000 copies/cell, has unusual gating properties, and is permeable to a range of anions and nutrients known to be required for parasite growth. We proposed that PSAC mediates the first step in a sequential diffusive pathway of nutrient acquisition. Current projects in the lab include: 1) characterizing the mechanism of permeation through PSAC, 2) developing and testing specific PSAC blockers that may function as future antimalarials, 3) cloning the gene(s) encoding PSAC and other transporters, and 4) heterologous expression of these transporters. These projects aim to understand the parasite's physiology and develop new strategies for control of malaria.