University of Zurich
Group leader
Senior Researcher
Senior Researcher
Researcher
Researcher
Researcher
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 for applications in
biotechnology, to inhibit other
proteins or to kill tumor cells in therapy, or the stabilization of proteins so that they
can be studied structurally
and biophysically, such as G-protein-coupled receptors evolved to high stability and
expression levels for drug
screening and structural studies.
One of our main areas of interest have been novel
scaffolds for selective binding
(e.g. the DARPin technology we have developed), or other repeat proteins such as the
Armadillo Repeat Proteins.
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.
In most projects also structure determination is needed by crystallography carried out in
the research group,
or in collaboration, by NMR or cryo electron tomography.
Some projects also bridge
protein engineering with
applications, in cell biology or, in the case of tumor targeting testing in animal models.
Michel E., Cucuzza S., Mittl P.R.E., Zerbe O., and Plückthun A. (2023) Improved Repeat Protein Stability by Combined Consensus and Computational Protein Design Biochemistry 62 (2), 318-329 doi: 10.1021/acs.biochem.2c00083
Hansen, S., Ernst, P., König, S. L. B., Reichen, C., Ewald, C., Nettels, D., Mittl, P. R. E., Schuler, B. and Plückthun, A. (2018) Curvature of designed armadillo repeat proteins allows modular peptide binding. J. Struct. Biol. 201, 108-117.
Hansen, S., Kiefer, J. D., Madhurantakam, C., Mittl, P. R. E. and Plückthun, A. (2017) Structures of designed armadillo repeat proteins binding to peptides fused to globular domains. Protein Sci. 26, 1942-1952.
Ernst, P. and Plückthun, A. (2017) Advances in the design and engineering of peptide-binding repeat proteins. Biol. Chem. 398, 23-29.