Trypanosome molecules and host-parasite-vector interactions

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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.