MEMBRANE TRAFFICKING IN MALARIA INFECTED ERYTHROCYTES

疟疾仍然是热带世界的一个祸害， 每年有100万人死亡，约200万人死亡。的进化 抗氯喹恶性疟原虫株和有效疟疾 疫苗仍需多年，基于最新发展的新战略 在疟疾寄生虫的生物化学中可能打开药理学的大门， 这种地方病的化疗。症状性疟疾 是由无性寄生虫引起的， 疟疾生命周期的一个阶段。1）干扰过程， 裂殖子侵入红细胞的生化机制， 控制寄生虫的细胞内成熟和增殖， 为了生存，可以阻止或改善这种疾病。朝着这个 最后，本文将探讨三个具体目标：第一，入侵机制 将通过标记感染性分生孢子和/或 红细胞与荧光磷脂，并观察事件， 蒸发;（即，脂质交换，红细胞内陷， 等等）。通过激光扫描共聚焦荧光成像显微镜（CSCMS）。 使用这种技术，荧光的可视化， 掺入裂殖子中的荧光磷脂， 红细胞膜允许检查侵入事件， 单细胞水平。卡西尼号还将明确显示 寄生空泡膜（PVM）。阶段特异性恶性疟原虫 受感染的红细胞将被不同荧光脂质标记， 类，以确定脂质运输或分类之间的途径， 红细胞、PVM和寄生虫膜。荧光成像显微术 将有助于识别感染的新膜结构 红细胞质抗疟药对脂质摄取的影响， 合成和膜运输也将进行研究，以更好地 了解他们的行动方式。这些新战略的实施， 疟疾的新技术将使人们对（膜） 这种疾病的生物化学，并可能最终提供基本的 新的抗疟疾化疗药物和治疗的开发 养生法

Malaria continues to be a scourge on the tropical world, afflicting 200-300 million people a year, killing about 2 million. With the evolution of chloroquine-resistant strains of P. falciparum and efficacious malaria vaccines still many years away, new strategies based on recent developments in the biochemistry of malarial parasites may open pharmacological inroads into the chemotherapy of this endemic disease. Symptomatic malarial disease is cause by asexual parasites that proliferate during the erythrocytic stage of the malarial life cycle. Interference with 1) the process by which a merozoite invades an erythrocyte of 2) the biochemical mechanisms which govern intracellular maturation and proliferation of the parasite which are obligate for survival, could arrest or ameliorate this disease. Toward this end, three specific aims will be pursued firstly, the mechanism of invasion of the erythrocyte will be probed by labeling infectious merzoites and/or erythrocytes with fluorescent phopholipids and observing the events which transpire; (i, e., exchange of lipid, invagination of the erythrocyte, etc.) by laser-scanning confocal fluorescence imaging microscopy (CFIM). using this technique, visualization of the fluorescence which arises from the fluorescent phopholipids incorporated into the merozoite and erythrocyte membranes allows examination of the invasion event at the single cell level. CFIM will also definitively show the origin of the parasitophorous vacuole membrane (PVM). Stage-specific P. falciparum infected erythrocytes will be labeled with fluorescent lipids of varying class to identify the lipid trafficking or sorting pathways between the erythrocyte, PVM and parasite membranes. Fluorescence imaging microscopy will aid in the identification of new membranous structures in the infected erythrocyte cytoplasm. The effects of anti-malarial agents on lipid uptake, synthesis and membrane trafficking will also be investigated to better understand their mode of action. Application of these new strategies and techniques to malaria will give considerable new insight into (membrane) biochemistry of this disease and may ultimately provide the basic for the development of new anti-malarial chemotherapeutic agents and treatment regimens.