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-mediated 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 are currently engaged in optimizing RNAi protocols in different schistosome life cycle stages. This work aims to facilitate functional genomics in schistosomes.
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 (SGTPs) and amino acid permeases (SPRM1) and we currently continue to characterize these and other surface-exposed parasite proteins. Vaccine studies will be undertaken to test the hypothesis that immunization schemes that induce immune recognition of such nutrient-importing proteins will enable the host to eliminate the parasites and prevent infection. Vaccine studies are being undertaken with our collaborator Professor Rashika El Ridi at the Department of Zoology, Cairo University, Egypt.B. In vivo panning for schistosome protective epitopes
This research is designed to identify new targets of protective immunity. In this work we use in vivo 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 will be detected and identified using non-immune phage display libraries or libraries derived from immunized animals. Molecules expressing these epitopes will be characterized and may be tested in vaccine trials. Recombinant antibodies will be engineered from selected scFvs to test their protective potential in vivo within the permissive mouse model.