The main objective of this project is the development of methods for genetic manipulation of the human parasite Schistosoma mansoni. We will focus on the transposable elements Sleeping Beauty and mariner to mediate stable genomic integration and expression of transgenes in schistosomes. The foreign DNA will be introduced into the parasites by particle bombardment. In preliminary studies we have already shown that simple DNA constructs can be introduced into adult worms, and into the larval stages, the sporocysts and miracidia. Using this method, we have achieved (transient) expression of the reporter gene EGFP in schistosomes. We could also show that after transfection of miracidia the transgene was actively expressed in the next larval stage, the sporocyst, and that transfected miracidia could be used to infect the intermediate snail host. We now hope to achieve stable transgene integration using mobile genetic elements, whose mobility inherently relies on chromosomal integration.The ultimate aim is to target essential biochemical pathways in these parasites using reverse genetics approaches designed to explore their biological function and value as targets for intervention strategies.
DFG Programme
Research Grants
