IMIB - Institute for Molecular Infection Biology

Molecular characterization of the wnt-signaling pathway in Echinococcus multilocularis

Human alveolar echinococcosis is a severe neglected disease, caused by tumor-like growth of the metacestode larval stage of the fox-tapeworm Echinococcus multilocularis. Diagnosis often only occurs after decades and treatment is usually limited to life-long chemotherapy. Infiltrative, cancer-like growth of the metacestode results from a unique and Echinococcus-specific developmental event: the invading oncosphere larva literally ‘shuts down’ the anterior body pole (head) and subsequently grows as posteriorized tissue into the organs of the host. Later during development, numerous ‘heads’ are reactivated within the metacestode tissue, leading to larvae (protoscolices) that are infective for the definitive host.

These developmental transitions are caused by modulation of the parasite’s wnt-signaling pathway which, in all metazoans, determines anterior-posterior axis formation. We previously showed that WNT signaling factors, secreted by muscle cells, influence proliferation and differentiation of the Echinococcus germinative cells, which are totipotent somatic stem cells that crucially drive parasite development. In the present project, the precise influence of wnt-signaling components on germinative cell proliferation and differentiation, including cross-interaction with additional signaling pathways (e.g. insulin, TGF-beta, FGF-signaling) that drive parasite development, will be studied. To this end, sophisticated culture systems for parasite cell culture as well as functional genomic tools (e.g. RNA-interference) will be employed.