TKS Laboratory Research Summary

The Terry K. Smith laboratory has four main areas of research: biosynthesis and uptake of phospholipids in protozoan parasites; the enzymology of glycosyltransferases and other biosynthetic enzymes; the structure, function and biosynthesis of parasite glycoconjugates and glycosylphosphatidylinositol membrane anchors of eukaryotic cells

TKS Laboratory Research Description

There are currently no effective treatments against many of the debilitating and fatal diseases caused by insect-transmitted protozoan parasites such as Trypanosoma brucei (causative agent of African sleeping sickness), Trypanosoma cruzi (Chagas Disease), Leshmania (Leishmaniasis), Plasmodium (malaria) and Toxoplasma (Toxoplasmosis).

The cell-surface of these single-celled parasitic organisms are covered in glycosylphosphatidylinositol (GPI) anchors and related molecules. In T. brucei the biosynthesis of GPI anchors is required for their abundant variant surface glycoprotein which protects them against the harsh environment of the bloodstream. This GPI anchor biosynthesis is a proven genetic and chemical target for therapeutic drugs. Our research is concerned with the biosynthetic pathways of the building blocks required for GPI assembly (PI, PE, Dol-P-Man and other related phospho- and glyco-lipids). We are finding significant exploitable differences between human and parasitic biosynthetic pathways and enzymes. Inhibitor studies and chemical synthesis followed by screening of focussed compounds libraries for lead compounds will ultimately result in therapeutic drugs against these Third World diseases.