We study the creation of new proteins and protein variants. The purpose of this work is to use such engineered proteins to enable research and applications which have been very difficult or even impossible so far. Examples of our endeavors are the creation of new engineered binding proteins to inhibit other proteins or to kill tumor cells, or the stabilization of proteins so that they can be studied structurally and biophysically.
Our main areas of interest are novel scaffolds for selective binding (e.g. the DARPin technology we have developed), synthetic antibodies and G-protein-coupled receptors evolved to high stability and expression levels. Because of the complexity of these tasks, this research requires a highly interdisciplinary approach, combining detailed biophysical studies, computer modeling and advanced molecular biology, especially directed evolution. Many projects have close collaboration with crystallography, NMR or computational biology. Some projects also bridge protein engineering with applications, in cell biology or, in the case of tumor targeting testing in animal models.
Role of UZH within the “Dartrix Consortium”
Our part in Dartrix is the protein engineering.
Schematic depiction of a DARPin over tumor tissue stained with it.
Our current investors
The Swiss National Science Foundation
European Research Council
The Swiss Initiative in Systems Biology
Stefan, N., Martin-Killias, P., Wyss-Stoeckle, S., Honegger, A., Zangemeister-Wittke, U., and Plückthun, A. (2011). DARPins Recognizing the Tumor-Associated Antigen EpCAM Selected by Phage and Ribosome Display and Engineered for Multivalency. J. Mol. Biol. 826-843.
Martin-Killias, P., Stefan, N., Rothschild, S., Plückthun, A., and Zangemeister-Wittke, U. (2011). A novel fusion toxin derived from an EpCAM-specific designed ankyrin repeat protein has potent antitumor activity. Clin. Cancer Res. 17, 100-110.
Zahnd, C., Kawe, M., Stumpp, M. T., de Pasquale, C., Tamaskovic, R., Nagy-Davidescu, G., Dreier, B., Schibli, R., Binz, H. K., Waibel, R., and Plückthun, A. (2010). Efficient tumor targeting with high-affinity designed ankyrin repeat proteins: effects of affinity and molecular size. Cancer Res. 70, 1595-1605.
Zahnd, C., Wyler, E., Schwenk, J. M., Steiner, D., Lawrence, M. C., McKern, N. M., Pecorari, F., Ward, C. W., Joos, T. O., and Plückthun, A. (2007). A designed ankyrin repeat protein evolved to picomolar affinity to Her2. J Mol Biol 369, 1015-1028.
Binz, H. K., Amstutz, P., Kohl, A., Stumpp, M. T., Briand, C., Forrer, P., Grütter, M. G., and Plückthun, A. (2004). High-affinity binders selected from designed ankyrin repeat protein libraries. Nat Biotechnol 22, 575-582.
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