The Plasmodial Surface Anion Channel And Malaria Parasit

Apicomplexan分子生理学单位对离子和营养物质穿过感染疟疾寄生虫的人类红细胞的各种膜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、各种转运测定、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来鉴定感染恶性疟原虫的人类红细胞上的一种不寻常的离子通道，恶性疟原虫是最致命的疟疾。这种通道，疟原虫表面阴离子通道（PSAC），是目前在1000个拷贝/细胞，具有不寻常的门控特性，并渗透到一系列的阴离子和营养素已知所需的寄生虫生长。我们提出，PSAC介导的第一步，在一个连续的扩散途径的养分收购。实验室目前的项目包括：1）表征通过PSAC的渗透机制，2）开发和测试可能作为未来抗疟药的特异性PSAC阻断剂，3）克隆编码PSAC和其他转运蛋白的基因，以及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.