Trypanosome molecules and host-parasite-vector interactions

非洲锥虫是引起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，该蛋白质在整个寄生虫上形成致密的表面涂层。VSG库是大的，并允许血流形式的寄生虫，以避免消除从受感染的宿主哺乳动物的抗原变异现象。 由于VSG外壳带来的僵局，尽管经过了100多年的科学努力，但在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生物学，生物化学和免疫学的非洲锥虫在感染宿主哺乳动物和他们的采采蝇载体。 通过在分子水平上理解寄生虫-宿主和寄生虫-载体的相互作用，将有可能设计影响寄生虫存活和/或传播的策略。 我提议的研究将依赖于新开发的分子技术，这些技术可以识别和表征寄生虫蛋白质，这些蛋白质只存在于消失的少量中。 我的研究目标是：[1]研究刚果锥虫蛋白质组学分析中发现的新的锥虫蛋白和阶段调节蛋白的种特异性、生活史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。 拟议的研究将涉及在实验室中生长各种物种和锥虫的生命周期阶段，以及衍生出对锥虫蛋白特异性的抗体，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昆虫媒介传播疾病，并可能导致诊断和控制疾病的新策略的发展。

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.