The Molecular Helminthology Laboratory is currently engaged in several research projects involving schistosomes.
1. RNA interference (RNAi) in schistosomes
Large scale genome sequencing is being done by international consortia for each of the three major human schistosome species: Schistosoma mansoni, S. hematobium and S. japonicum. A major project in our laboratory is to develop useful molecular tools that will allow us to exploit the sequence data that is being generated. We have used RNA interference (RNAi), or post-transcriptional gene silencing, to inhibit gene expression in schistosomes by treating them with double-stranded RNA. By suppressing gene expression in this manner, we can explore the function of selected genes. We have optimized RNAi protocols in different schistosome life cycle stages and have begun to use the methodology for functional genomics in schistosomes with particular emphasis on the host-interactive parasite surface
2. The host-interactive schistosome surface
The schistosome surface is the site of intimate host/parasite interaction; nutrients are taken up across the body surface of parasites in the bloodstream and environmental sensing occurs at the surface. There is great interest in identifying and characterizing molecules at the host-exposed parasite surface for two main reasons; first, in order to gain a better understanding of surface biochemistry and cell biology and second, since molecules exposed at the parasite surface should be accessible to host immune effectors and therefore could be used as vaccine targets to evoke protective immunity. Our laboratory has a long history of research work on schistosome surface biochemistry. Two major projects that focus on the schistosome surface are currently being undertaken in the laboratory:
A. Cloning and characterization of schistosome surface molecules
While schistosomes possess a functional mouth and gut, most nutrients are imported across the parasite's body surface (or tegument). We have cloned cDNAs encoding several nutrient-importing proteins, notably glucose transporter proteins and amino acid permeases. We continue to characterize surface-exposed parasite proteins as they are identified by proteomic or phage display methods (below). We are currently testing hypotheses that these host-exposed proteins, in addition to nutrient uptake, are important in immune evasion, in metabolite exchange and in transducing signals from the host.B. In vivo panning for schistosome protective epitopes
This research is designed to identify new targets of protective immunity. In this work we use phage display technology to identify single-chain antibodies (scFvs) able to bind to the surface of schistosomes as they reside within their host. Host-exposed schistosome epitopes are detected and identified using phage display scFv libraries derived from animals that mount protective immune responses to schistosomes, particularly the Fisher rat. Molecules expressing these epitopes will be characterized and may be tested in vaccine trials.