MEMBRANE TRAFFICKING IN MALARIA INFECTED ERYTHROCYTES

疟疾仍然是热带世界的祸害，使200-300人深受其害。 每年有100万人死亡，大约有200万人死亡。随着时间的推移 恶性疟原虫氯喹抗性株与有效疟疾 疫苗仍然需要很多年，根据最近的发展制定新的战略 在疟疾的生物化学方面，寄生虫可能会打开药理学的大门 用于这种地方病的化疗。症状性疟疾 是由红血球期间繁殖的无性寄生虫引起 疟疾生命周期的一个阶段。对1)过程的干扰 裂殖子侵入红血球的生化机制 控制寄生虫的细胞内成熟和增殖，这是 对生存的义务，可以阻止或改善这种疾病。朝向这个方向 最后，我们将首先探讨三个具体目标：入侵机制 将通过标记有传染性的分生孢子和/或 用荧光磷脂标记红细胞，观察 排出；(即，脂质交换，红细胞内陷， 等)激光扫描共聚焦荧光成像显微镜(CFIm)。 使用这项技术，可视化的荧光产生于 荧光磷脂被结合到裂殖子和 红细胞膜可以检查入侵事件在 单细胞水平。CFIM还将明确显示 寄生性液泡膜(PVM)。特定阶段恶性疟原虫 被感染的红细胞将被标记不同的荧光脂类 类来标识 红细胞膜、PVM和寄生虫膜。荧光成像显微镜 将有助于识别感染的患者体内新的膜结构 红细胞胞浆。抗疟疾药物对脂质摄取的影响， 合成和膜运输也将进行调查，以更好地 了解他们的行动模式。这些新战略的应用和 防治疟疾的技术将为(膜)提供相当大的新见解 这种疾病的生物化学，并最终可能为 新型抗疟疾化疗药物及其治疗的研究进展 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.