Trypanosome molecules and host-parasite-vector interactions

锥虫分子和宿主-寄生虫-载体相互作用

• 批准号: 8405-2013
• 负责人: Pearson, Terry
• 金额: $ 2.62万
• 依托单位: University of Victoria
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=544513
• 关键词: Trypanosome; molecules; host; parasite; vector

African trypanosomes, the parasites that cause African sleeping sickness in humans and similar diseases in domestic animals, cause severe socioeconomic problems in sub-Saharan Africa. These parasites are spread by the infamous tsetse flies and have evolved mechanisms to avoid rejection by the host's immune system. They do this by expressing an abundant protein called the variant surface glycoprotein (VSG) which forms a dense surface coat over the entire parasite. The VSG repertoire is large and allows bloodstream forms of the parasite to avoid elimination from an infected host mammal by the phenomenon of antigenic variation. Because of the impasse presented by the VSG coat, no vaccine candidates have been identified in African trypanosomes, despite more than 100 years of scientific effort. The major goal of my research program is to understand the biology, biochemistry and immunology of the African trypanosomes in infected host mammals and in their tsetse fly vectors. By understanding parasite-host and parasite-vector interactions at a molecular level it will be possible to devise strategies for influencing parasite survival and/or transmission. My proposed research will rely on newly developed molecular techniques that allow the identification and characterization of parasite proteins that are only present in vanishingly small quantities. My research objectives are: [1] To study the species specificity, life cycle stage expression and subcellular localization of selected, newly identified trypanosome proteins and stage regulated proteins discovered by our proteomic analysis of Trypanosoma congolense. [2] To identity trypanosome molecules in the plasma of mammals with early- and late-stage infections and to develop sensitive assays for measuring selected proteins. The proposed research will involve growth in the lab of a variety of species and life cycle stages of trypanosomes and the derivation of antibodies specific for trypanosome proteins which allow us to detect and measure them. Knowledge gained from our research will aid in our understanding of disease transmission by insect vectors and may lead to development of new strategies for diagnosis and control of disease.

非洲锥虫是一种导致人类非洲昏睡病和家畜类似疾病的寄生虫，在撒哈拉以南非洲地区造成严重的社会经济问题。 这些寄生虫由臭名昭著的采采蝇传播，并已进化出避免宿主免疫系统排斥的机制。 它们通过表达一种称为变异表面糖蛋白（VSG）的丰富蛋白质来做到这一点，这种蛋白质在整个寄生虫上形成致密的表面涂层。 VSG 库很大，允许血流形式的寄生虫避免通过抗原变异现象从受感染的宿主哺乳动物中消除。 由于 VSG 外壳造成的僵局，尽管经过 100 多年的科学努力，仍未在非洲锥虫中鉴定出候选疫苗。 我的研究项目的主要目标是了解受感染宿主哺乳动物及其采采蝇载体中非洲锥虫的生物学、生物化学和免疫学。 通过在分子水平上了解寄生虫-宿主和寄生虫-载体相互作用，将有可能设计出影响寄生虫生存和/或传播的策略。 我提出的研究将依赖于新开发的分子技术，该技术可以识别和表征仅以极少量存在的寄生虫蛋白质。 我的研究目标是： [1] 研究通过我们对刚果锥虫的蛋白质组学分析发现的选定的、新鉴定的锥虫蛋白和阶段调节蛋白的物种特异性、生命周期阶段表达和亚细胞定位。 [2] 鉴定早期和晚期感染哺乳动物血浆中的锥虫分子，并开发用于测量选定蛋白质的灵敏测定法。 拟议的研究将涉及锥虫的各种物种和生命周期阶段的实验室生长，以及锥虫蛋白特异性抗体的衍生，使我们能够检测和测量它们。 从我们的研究中获得的知识将有助于我们了解昆虫媒介传播疾病，并可能导致开发疾病诊断和控制的新策略。