Plasmodial Surface Anion Channel And Malaria Parasite

疟原虫表面阴离子通道与疟原虫

• 批准号: 6503692
• 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/6503692
• 关键词: Plasmodium falciparum; antimalarial agents; biological transport; drug screening /evaluation; electrophysiology; membrane channels; membrane transport proteins; microorganism culture; microorganism metabolism; molecular cloning; nutrient interaction; protozoal genetics

The Malaria Molecular Physiology Section conducts basic research on the transport of ions and nutrients across various membranes of the malaria parasite or its host cells. This work incorporates molecular biology and informatics, protein and lipid biochemistry, and biophysics. We recently used electrophyiological methods to identify an unusual ion channel on human red blood cells infected with P. falciparum which causes a severe 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 with various transport methods, 2) developing and testing specific PSAC blockers that may function as future antimalarials, 3) cloning the genes of various parasite 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.

疟疾分子生理科对离子和营养物质在疟疾寄生虫或其宿主细胞的各种膜上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，以及生物物理学。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，恶性疟原虫会导致一种严重的疟疾。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)研究不同转运方式下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)克隆各种寄生虫转运蛋白的基因；4)异源表达这些转运蛋白。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。