Trypanosome molecules and host-parasite-vector interactions

非洲锥虫是一种寄生虫，在人类身上引起非洲昏睡病，在家畜中引起类似的疾病，在撒哈拉以南非洲造成严重的社会经济问题。这些寄生虫是由臭名昭著的采采蝇传播的，并进化出了避免宿主免疫系统排斥的机制。它们通过表达一种名为变异表面糖蛋白(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了一层致密的表面涂层。VSG谱系很大，允许血液形式的寄生虫避免因抗原变异现象而从受感染的宿主哺乳动物中消除。由于VSG外衣造成的僵局，尽管进行了100多年的科学努力，非洲锥虫中还没有发现候选疫苗。我的研究计划的主要目标是了解非洲锥虫在受感染的宿主哺乳动物及其采采蝇媒介中的生物学、生化和免疫学。通过在分子水平上了解寄生虫-宿主和寄生虫-病媒的相互作用，将有可能设计出影响寄生虫生存和/或传播的策略。我提议的研究将依赖于新开发的分子技术，这些技术允许识别和表征只存在于极少量的寄生虫蛋白质。我的研究目标是：[1]研究我们在蛋白组学分析中发现的锥虫新发现的锥虫蛋白和阶段调控蛋白的物种特异性、生活史阶段表达和亚细胞定位。[2]鉴定患有早期和晚期感染的哺乳动物血浆中的锥虫分子，并建立灵敏的检测选定蛋白质的方法。拟议的研究将涉及在实验室中培养各种种类和生命周期阶段的锥虫，以及衍生针对锥体蛋白的抗体，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通过昆虫媒介传播疾病的情况，并可能导致开发新的疾病诊断和控制策略。

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.