The surface of parasites is ‘coated’ with molecules (see How does gene expression affect parasite success? for more information). During an infection, these molecules help the parasite evade the immune system. These surface molecules also help the parasite to proliferate inside the insects that carry the parasite and successfully initial infect the human host. Because this ‘coat’ is so important for survival, medicines that interfere with the construction of this coat can kill the parasite. Mike Ferguson’s lab is working to define the structure of parasite surface molecules and identify the parasite genes and enzymes required to build them.
In trypanosomatid parasites, most of these molecules are glycosylphosphatidylinositol (GPI) anchored glycoproteins or GPI-related glycolipids. The “GPI” part of the molecule anchors the entire structure to the surface of the parasite. The rest of the molecule contains a diverse combination of proteins and sugars. These may be branched, repeating, and highly modified. The combination and pattern of these components make these surface molecules unique to the parasite. The basic structure of these molecules is known. We want to understand how these molecules are so successful at helping the parasite survive. Recently we helped discover that one of the surface molecules of T. brucei, VSG3, contains O-glycosylation modifications that increase parasite virulence (Read paper).
To discover the structure of surface molecules and then to explore their role in parasite biology, the Ferguson lab uses a multidisciplinary approach including; mass spectrometry, bioinformatic analysis, enzymology, and genetics.
By understanding which enzymes are required to build these molecules we can identify new anti-parasite medicines. We are using mass spectrometry to characterised undescribed proteins (Read paper), especially those that occur in complexes (Read paper). This is providing new starting points for drug discovery and creating a valuable resource for parasite biology.