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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：
7686863
负责人：
anthony holder
金额：
$ 57.9万
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/7686863
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.

该应用程序旨在解决疟疾相关贫血的分子基础，疟疾寄生虫感染的流行和往往危及生命的表现。数亿的人有临床疟疾感染，因此，该疾病对人类健康的影响，深刻在寄生虫侵入红细胞使其繁殖的过程中，寄生虫分子与这些细胞的表面结合。有人提出，这些分子，这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，清除未感染的红细胞，从而导致贫血。此外，建议测试这一假说认为，针对这些分子的特异性抗体促进了这种清除。双分子复合物将检查由与宿主红细胞结合有关的丰富蛋白质组成的蛋白质，确定其结构、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被阐明。它们与红细胞分子的特异性相互作用膜将被定义，并在实地研究中检查其加剧贫血的潜力。的寄生虫系的特性，其中特定的基因，编码这些分子之一的成分，复合物，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- 主机平衡。有人提出，这些基因操纵的寄生虫可以扰乱机制，维持红细胞平衡，导致红细胞数量控制功能失调，贫血重要的是要确定作为潜在的疟疾疫苗候选物的分子是否也是促进贫血的免疫机制的目标。