The Plasmodial Surface Anion Channel And Malaria Parasit

疟原虫表面阴离子通道与疟原虫

• 批准号: 6809114
• 负责人: SANJAY A DESAI
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6809114
• 关键词: Plasmodium falciparum; SDS polyacrylamide gel electrophoresis; Xenopus oocyte; antimalarial agents; biological transport; biophysics; drug screening /evaluation; electrophysiology; erythrocytes; high throughput technology; ion transport; matrix assisted laser desorption ionization; membrane channels; membrane transport proteins; microorganism culture; microorganism metabolism; molecular cloning; nutrient interaction; protozoal genetics

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.

Apicomplexan分子生理学单位对感染疟疾寄生虫的人类红血球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、蛋白质和脂肪生物化学、各种转运分析、生物物理学和高通量化合物文库筛选。最近，我们使用电生理学方法识别了感染恶性疟原虫的人红细胞上一种不寻常的离子通道，恶性疟原虫是最致命的疟疾形式。这种通道，即原生物质表面阴离子通道(PSAC)，存在于1000个拷贝/细胞中，具有不同寻常的门控特性，可以渗透到一系列已知的寄生虫生长所需的阴离子和营养物质中。我们认为PSAC介导了营养获得的连续扩散途径的第一步。实验室目前的工作包括：1)确定PSAC的渗透机制；2)开发和测试未来可能作为抗疟疾药物的特定PSAC阻滞剂；3)克隆编码PSAC和其他转运蛋白的基因(S)，以及4)这些转运蛋白的异源表达。这些项目旨在了解这种寄生虫的生理并制定控制疟疾的新战略。