Malarial proteins in erythrocyte adhesion and dyserthropoiesis

红细胞粘附和红细胞生成障碍中的疟疾蛋白

基本信息

批准号：
7538847
负责人：
anthony holder
金额：
$ 57.41万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7538847
关键词：
Address Adhesions Anemia Antibodies Antibody Specificity Antigens Apical Binding Binding Proteins Biological Assay Biology Causations Cell Count Cell surface Cells Chemicals Clinical Code Complement Complex Detection Disease Disruption Dissection Endopeptidases Equilibrium Erythrocyte Membrane Erythrocytes Erythropoiesis Excision Family Gene Components Gene Family Genes Genetic Glycocalyx Growth Health Human Immune Immune Targeting Immune response Immunity In Vitro Incubated Individual Infection Invaded Knock-out Label Life Malaria Malaria Vaccines Maps Mediating Membrane Merozoite Surface Protein 1 Molecular Monoclonal Antibodies Numbers Organelles Parasites Pathway interactions Peptide Hydrolases Phagocytosis Phenotype Plasmodium berghei Process Property Protein Binding Proteins Proteolytic Processing Rate Research Personnel Reticulocytes Role Silicone Oils Specificity Structure Surface Techniques Testing Transgenic Mice Work base design fluorescence activated cell sorter device homologous recombination in vivo member polypeptide programs receptor rhoptry senescence

项目摘要

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.

该应用旨在解决与疟疾相关性贫血的分子基础，这是最多的贫血之一疟原虫寄生虫感染的流行，常常威胁生命的表现。亿万人们每年都有临床疟疾感染，因此该疾病对人类健康的影响是深刻的。在寄生虫入侵红细胞的过程中寄生虫分子与这些细胞的表面结合。有人提出这些分子也是从寄生虫中脱下，与感染宿主中未感染的红细胞结合，并促进破坏和未感染的红细胞的清除，从而导致贫血。此外，提议测试假设对此类分子的特定抗体促进了这种清除率。两个分子复合物由涉及与宿主红细胞结合的丰富蛋白质组成定义它们的结构，多样性和功能。负责与红细胞及其结合的组件将阐明红细胞侵袭中的作用。它们与红细胞分子的特定相互作用膜将被定义，并在基于现场的研究中检查其对脑症的较大贫血。这寄生虫线的特性，其中特定基因编码这些分子之一的成分复合物已被删除。这些修饰的寄生虫的表型可能是表示为宿主细胞特异性或不同生长速率的变化，或者是寄生虫的改变主机余额。有人提出，这些遗传操纵的寄生虫会干扰的机制保持红细胞平衡，导致对红细胞数量的功能失调，因此贫血。确定候选疟疾疫苗的分子是否是也是促进贫血的免疫机制的靶标。