Student projects at the University of Zurich

At the University Cildren’s Hospital Zürich Tumor targeting

Current the rapies for rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, can be improved by delivering drugs specifically to the tumour. Tumour targeting peptides promise to be an excellent tool to deliver drugs to tumours in vivo. We have established a phage display-based screening system for identification of RMS-specific binding peptides, and have identified several peptide sequences that bind preferentially to tumour cells in vitro as well as in vivo. We have identified proprotein convertases (PCs) as potential target for binding of several selected targeting peptides. PCs play a central role in activation of several molecules involved in cancer progression and metastasis. Indeed, inhibition of furin activity, the most prominent PC, was shown to block cancer progression in gastric carcinomas mouse models.
Several open questions are available for students as project and master work.

1. The role of furin and PC7, the only two PCs found to be consistently expressed in RMS has to be studied by overexpression/silencing in cell culture. In particular, the effect on processing of pro-angiogenic molecules will be evaluated by conventional techniques (westen blotting) and functional in vitro assays (cell migration, invasion).

2. The mechanism of targeting specificity has to be investigated. Notably, PCs are mainly localized in the golgi/trans-golgi compartments. Furin and PC7 can be localized on the cell surface. The mechanisms regulating differential cellular localization are largely unknown. Understanding these mechanisms might help improve in vivo targeting of furin. This project will involve cell culture, microscopy (conventional and confocal), production of furin mutants, functional enzyme assays.

The work will be carried out at the Experimentelle Infektiologie und Krebsforschung des Kinderspital Zurich, August Forel Strasse 1, 8008 Zurich.
Contact person:Michele Bernasconi
www.eicr.uzh.ch