Molecular Analysis of PFEMP1 Binding Activity

描述：(申请人提供)：估计疟原虫 每年有一两百万人死于恶性疟疾。虽然大多数感染是 不致命的严重疾病发生在感染的红细胞隔离和 积聚在重要器官中，如大脑和胎盘。通过对P. 恶性疟原虫红细胞膜蛋白1(PfEMP1)家族在 感染的红细胞隔离。PftMP1是结合配体， 输出到红细胞表面。PfEMP1具有不同的结合特异性 并被认为决定了受感染的解剖分布 红细胞和疾病转归。 为了探索PfEMP1在疟疾发病机制中的作用，我们将研究三个 感染红细胞与CD36、细胞间黏附的结合特性 黏附分子1(ICAM-1)和硫酸软骨素A(CsA)已被 与疟疾有关。CD36是血管内皮细胞的主要受体 寄生虫隔离。ICAM-1和CsA被认为与脑和 分别为胎盘隔离症。其中每一个的PfEMP1结合域 受体已经被定义。据估计，每种寄生虫菌株都有 大约50种不同的PfEMP1。我们计划进行全基因组调查 PfEMPI结合，高通量检测，重点是3D7寄生虫 这是疟疾基因组计划的主题。来自这些的发现 调查将评估绑定属性被编码的程度 并在基因组中的大麻1之间保守，这将为深入了解 恶性疟原虫的致病潜能。

DESCRIPTION: (provided by the applicant): It is estimated that Plasmodium falciparumkills one to two million people each year. While most infections are not lethal, severe disease occurs when infected erythrocytes sequester and accumulate in vital organs, such as brain and placenta. The P. falciparumerythrocyte membrane protein 1 (PfEMP1) family has a critical role in infected erythrocyte sequestration. PftMP1 are binding ligands that are exported to the erythrocyte surface. PfEMP1 have different binding specificity and are believed to determine the anatomic distribution of infected erythrocytes and disease outcome. To explore the role of PfEMP1 in malaria pathogenesis we will study three binding traits of infected erythrocytes, adhesion to CD36, to Intercellular adhesion molecule 1 (ICAM-1), and to chondroitin sulfate A (CSA) that have been implicated in malaria disease. CD36 is the major endothelial receptor for parasite sequestration. ICAM-1 and CSA have been implicated in cerebral and placental sequestration, respectively. PfEMP1 binding domains for each of these receptors have been defined. It is estimated that each parasite strain has approximately fifty different PfEMP1. We plan to perform whole genome surveys of PfEMPI binding, with high-throughput assays, focusing on the 3D7 parasite that is the subject of the Malaria Genome Project. Findings from these investigations will assess the extent to which binding properties are encoded and conserved between HEMP 1 in a genome and will provide insight into the pathogenic potential of P. falciparum.