MOLECULAR BASIS OF ANTIGENIC VARIATION ON MALARIA

疟疾抗原变异的分子基础

• 批准号: 7349173
• 负责人: MARY R GALINSKI
• 金额: $ 4.01万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-09 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349173
• 关键词: Macaca mulatta; antigens; gene expression; malaria; model

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The basic objective of this research is to understand the molecular mechanisms that govern variant antigen gene expression in Plasmodium. Antigenic variation is a fundamental adaptation to evade a host protective immune response and is one of the major factors contributing to the establishment of chronic blood infections. The classic P. knowlesi-rhesus monkey model of malaria is the primary focus of investigations. This simian malaria model is amenable to both in vitro and in vivo studies and unique stable clones of the P. knowlesi H strain expressing distinct SICA (Schizont Infected Cell Agglutination) variant antigen phenotypes after induced sequential switchings can be maintained after numerous in vivo passages (60 generations) in naive rhesus monkeys. These isogenic clonal lines provide a special tool for studies of the cellular and genetic mechanisms underlying clonal antigenic variation. Recently, we have also initiated complementary investigations on malaria variant antigens using the simian malaria, P. coatneyi, since this species has a similar periodicity, and morphological and immunopathophysiological characteristics that are comparable to the most severe human malaria, P. falciparum. Studies this past year have focused on continued genome wide analyses of the SICAvar gene family and studies developing molecular data relating to our hypothesis of post transcriptional gene silencing as a mechanism to control variant antigen gene expression.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究的基本目的是了解控制疟原虫变异抗原基因表达的分子机制。抗原变异是逃避宿主保护性免疫反应的基本适应，也是导致慢性血液感染的主要因素之一。典型的诺氏疟原虫-恒河猴疟疾模型是调查的主要焦点。这种猴疟疾模型适用于体外和体内研究，在幼猴体内多次传代(60代)后，表达不同SICA(Schizont感染性细胞凝集)变异抗原表型的诺氏疟原虫H株独特的稳定克隆仍能保持不变。这些等基因克隆系为研究克隆抗原变异的细胞和遗传机制提供了一种特殊的工具。最近，我们还利用猿猴疟疾Coatneyi启动了对疟疾变异抗原的补充研究，因为该物种具有类似的周期性，以及与人类最严重的疟疾恶性疟原虫相似的形态和免疫病理生理学特征。在过去的一年里，研究集中在对SICAvar基因家族的持续全基因组分析，以及与我们的转录后基因沉默作为控制变异抗原基因表达机制的假设相关的分子数据的研究。