This proposal looks at the immunological and molecular mechanism whereby trypanosomes evade the humoral immune response of their human host. Biochemical, Physical, Electron Microscope Image Reconstruction and Other Computer Techniques are used to elucidate the probable folding structure differences in variant specific glycoproteins (VSG) which could be responsible for antigenic variation at the molecular level. Thus work is co-ordinated with x-ray crystallographic studies on VSG structure being carried out elsewhere. The expression of VSG and other trypanosome structural genes involves a step not hitherto seen in other eukaryotes, wherby small RNA transcripts are spliced into trypansome mRNA. The nature of this mechanism at the molecular level is under investigation using recombinant DNA techniques. The control of VSG gene and other structural gene expression remains unknown in these parasites. We will set up a transformation system in trypanosomes in order to study gene expression. We are making functional trypansome mutants by selective and dominant marker genetic engineering techniques to serve as selection systems. The long-term aim is to understand the interaction of the host's immune system with the parasite, so that eventually the balance can be swung in favor of the host.
