Malarial proteins in erythrocyte adhesion and dyserthropoiesis

该应用旨在解决疟疾相关贫血的分子基础，疟疾是最常见的贫血之一。 疟疾寄生虫感染的普遍且常常危及生命的表现。数亿 每年有 10% 的人感染临床疟疾，因此该疾病对人类健康的影响是 深刻。在寄生虫侵入红细胞并使其在其中繁殖的过程中， 寄生虫分子结合到这些细胞的表面。据建议，这些分子也 从寄生虫中脱落，与受感染宿主中未受感染的红细胞结合并促进破坏和 清除未感染的红细胞，从而导致贫血。此外，建议测试 假设针对此类分子的特异性抗体会促进这种清除。两个分子复合物 由丰富的蛋白质组成，这些蛋白质与宿主红细胞的结合有关，将被检查 定义它们的结构、多样性和功能。负责与红细胞结合的成分及其 在红细胞侵袭中的作用将得到阐明。它们与红细胞分子的特定相互作用 膜将被定义，并在实地研究中检查它们加剧贫血的可能性。的 寄生虫品系的特性，其中特定基因编码这些分子之一的成分 复合体，已被删除将被研究。这些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，或不同的生长速率，或寄生虫的改变 主机余额。有人提出，这些基因操纵的寄生虫可能会扰乱以下机制： 维持红细胞平衡，导致红细胞数量控制功能失调，从而导致 贫血。确定潜在的疟疾疫苗候选分子是否是非常重要的 也是促进贫血的免疫机制的目标。

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.