Tubovesicular traffic induced in red cells in plasmodia

人类血液中的红细胞被疟疾寄生虫恶性疟原虫感染，导致所有 疾病的症状和病理。保守估计估计有2- 3亿人受到影响 每年有超过一百万儿童死于疟疾。日益增长的抗药性威胁 各种形式的疟疾造成了对新药的迫切需求。针对主机的独特功能， 寄生虫相互作用为新药和疫苗的开发提供了一种途径。恶性疟原虫 导致了最致命的人类疟疾恶性疟原虫的一个显著特征是它在一个 当它感染红细胞时，这种宿主细胞是非内吞性的，不内陷其血浆 膜的然而，恶性疟原虫在这些细胞中诱导膜内陷和空泡形成。因此 它必须诱导内吞机制来摄取溶质和大分子。长期目标是 建议是确定和表征红细胞内吞空泡的机制， 是由疟疾寄生虫引起的这些研究将有助于我们了解的基本生物学的 红细胞和寄生虫，从而有助于人类健康。利用转染的分子遗传工具， 基因组学结合高分辨率成像技术和生化亚细胞分级分析 将用于鉴定和纯化被募集到空泡中的红细胞膜成分， 评估它们与宿主和寄生虫来源的特定脂质和蛋白质组分的相互作用。的 消除寄生虫基因产物或表达突变寄生虫的转显性形式的结果 红细胞空泡形成基因、红细胞表面抗原表达、药物和毒素 将在体外培养物中评价吸收和寄生虫生长。这些研究可能对 了解针对红细胞膜缺陷的化学和免疫预防机制 以及一种主要的人类病原体的感染维持人体红细胞在循环中的功能，清除老化的红细胞， 必须仔细协调以优化组织氧气输送。这需要理解 红细胞膜功能。我们利用疟原虫作为探针来研究红细胞膜 功能及其通过寄生虫致病过程的调节。我们的研究旨在了解 为了更好地将药物和其他疗法靶向于红细胞膜缺陷以及这些细胞的感染 一种主要的人类病原体

Erythrocytes in human blood are infected by malaria parasite Plasmodium falciparum, resulting in all the symptoms and pathologies of the disease. Conservative estimates predict 2-300 million people are afflicted with malaria and over a million children die from the infection each year. The growing threat of drug resistant forms of malaria has created an urgent requirement for new drugs. Targeting unique features of host and parasite interactions provides one approach to new drug and vaccine development. Plasmodium falciparum causes the most virulent form of human malaria. A striking feature of P.falciparum is its development in a vacuole when it infects the erythrocyte. This host cell is non-endocytic and does not invaginate its plasma membrane. Yet P. falciparum induces both membrane invagination and vacuole formation in these cells. Thus it must induce endocytic mechanisms to take up solutes and macromolecules. The long term aim of this proposal is to identify and characterize the mechanisms by which endocytic vacuoles in erythrocytes can be induced by malaria parasites. The studies will contribute to our understanding of the basic biology of the erythrocyte and parasite, and thereby contribute to human health. Molecular, genetic tools using transfection, genomics combined with high resolution imaging techniques and biochemical subcellular fractionation assays will be used to identify and purify erythrocyte membrane components that are recruited into the vacuole and evauate their interactions with specific lipids and protein components of both host and parasite origin. The consequence of ablation parasite gene products or expression of transdominant forms of mutant parasite genes on erythrocyte vacuole formation, expression of antigens on the erythrocyte surface, drug and toxin uptake and parasite growth will be evaluated in vitro cultures. These studies maybe important for understanding mechanisms of chemo and immunprophylaxis directed against erythrocyte membrane defects as well infection by a major human pathogen. The maintenance of human erythrocyte function in circulation, clearance of older red cells and the production of new ones must all be carefully coordinated to optimize tissue oxygen delivery. This requires understanding of erythrocyte membrane function. We utilize malaria parasites as a probe to study erythrocyte membrane function and their modulation by parasite pathogenic processes. Our studies are aimed at understanding how to better target drugs and other therapies to erythrocyte membrane defects as well as infection of these cells by a major human pathogen.