Malarial proteins in erythrocyte adhesion and dyserthropoiesis

该应用程序旨在解决疟疾相关贫血的分子基础，疟疾相关贫血是 疟疾寄生虫感染的普遍表现，通常危及生命。数亿美元 的人每年都有临床疟疾感染，因此这种疾病对人类健康的影响是 很深刻。在寄生虫入侵红细胞以允许它们在体内繁殖的过程中， 寄生虫分子结合在这些细胞的表面。有人提出，这些分子，也是 从寄生虫中脱落，与感染宿主中未感染的红细胞结合，促进破坏和 清除未受感染的红细胞，从而导致贫血。此外，还建议测试 假设这些分子的特定抗体促进了这种清除。两种分子络合物 由与宿主红细胞结合有关的丰富蛋白质组成的将被检查以 确定它们的结构、多样性和功能。负责与红细胞结合的成分及其 在红细胞入侵中的作用将被阐明。它们与红细胞分子的特异性相互作用 将对膜进行定义，并在实地研究中检查其加重贫血的潜力。这个 寄生虫系的特性，在这些寄生虫系中编码这些分子之一的成分的特定基因 络合物，已被删除，将被研究。这些经修饰的寄生虫的表型可能是 表现为宿主细胞特异性的变化，或不同的生长速度，或寄生虫的变化- 主机余额。有人提出，这些基因操纵的寄生虫可以扰乱 维持红血球平衡，导致红血球数目控制失调，继而 贫血。重要的是要确定潜在的疟疾疫苗候选分子是否 也是促进贫血的免疫机制的靶标。

This application is designed to address the molecular basis of malaria-associated anemia, one of the most prevalent and often life-threatening manifestations of infection with the malaria parasite. Hundreds of millions of people have clinical malaria infections every year and thus the impact of the disease on human health is profound. During the process by which the parasites invade erythrocytesto allow them to multiply within, parasite molecules bind to the surface of these cells. It is proposed that these molecules, which are also shed from the parasite, bind to uninfected erythrocytes in the infected host and promote the destruction and clearance of uninfected red blood cells, thus contributing to anemia. Furthermore it is proposed to test the hypothesis that specific antibodies to such molecules promote this clearance. Two molecular complexes consisting of abundant proteins that have been implicated in binding to host erythrocytes will be examined to define their structure, diversity and function. The components responsible for binding to red cells and their role in red blood cell invasion will be clarified. Their specific interactions with molecules of the erythrocyte membrane will be defined, and their pontential to exacerbate anemia examined in field-based studies. The properties of parasite lines in which specific genes, coding for components of one of these molecular complexes, have been deleted will be studied. The phenotype of these modified parasites may be expressed as a change of host cell specificity, or different growth rate, or in an alteration of the parasite- host balance. It is proposed that these genetically manipulated parasites can disturb the mechanisms that maintain the red cell equilibrium, leading to dysfunctional control of red cell numbers and consequent anemia. It will be important to establish whether molecules that are potential malaria vaccine candidates are also the targets of immune mechanisms that promote anemia.