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The central theme of our research is to take advantage of the unique properties of proteins and peptides to develop new molecular tools that allow the imaging of molecular processes in live cells or organisms. Techniques and approaches from molecular biology and protein biochemistry are combined with synthetic (supramolecular) chemistry and various biophysical techniques. We believe that molecular understanding of complex biomolecular interactions is crucial for the successful development of these tools. Inspired by the modular design of natural signaling proteins, we are pursuing a protein engineering approach (plug and play protein engineering) in which functional protein domains are connected via flexible peptide linkers. Controlling the conformational states in these chimeric protein switches requires a quantitative description of domain-domain interactions and the conformational distribution of the linkers. Current topics include:
- Rational design of FRET-based sensor proteins for intracellular imaging of small molecules
- Development of switchable reporter enzymes for diagnostic applications
- Semi-synthetic multivalent proteins and peptides as high-affinity targeting ligands for molecular imaging and diagnostics.
- Development of ‘smart’ enzyme–activatable molecular imaging probes that target extracellular matrix remodelling and cell surface receptors on tumor cells