Objective Proteins that switch between distinct conformational states are ideal to monitor and control molecular processes within the complexity of living cells. Inspired by the modular design of natural signaling proteins, we are pursuing a true engineering approach towards the development of protein switches which we call ‘plug-and-play’ protein engineering. In this approach we explore generic strategies to translate molecular recognition in an input protein domain directly into a readable signal generated by an output protein domain.A comprehensive research program is proposed that explores 4 new design concepts for protein switches:1. FRET 3.0. A generic design concept for genetically encoded fluorescent sensors that does not depend on ligand-induced conformational changes in a receptor domain.2. FRET-bodies. Integration of FRET sensors and antibody technology. Libraries of FRET sensor proteins displaying CDR3-type loops on the donor and acceptor domains are displayed on yeast, allowing efficient high-throughput screening using FACS.3. ELISA in solution. An innovative and generic approach to translate antibody binding directly into an enzymatic activation step is proposed that takes advantage of the unique structural properties of antibodies4. Light-responsive protein switches. Ligand binding proteins will be developed whose affinity can be reversibly controlled by photoresponsive protein domains.An integral aspect of the research program is to combine rational design and directed evolution. Apart from developing generic engineering concepts for specific application areas, modeling tools will be developed that allow quantitative analysis and prediction of conformational stabilities for modular protein switches. The availability of these robust and generally applicable engineering strategies will proof beneficial to many areas of life sciences, providing essential tools for intracellular imaging, synthetic biology, and molecular diagnostics. Fields of science natural scienceschemical sciencesanalytical chemistryquantitative analysisnatural sciencesbiological sciencessynthetic biologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsengineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensors Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-PE5 - ERC Starting Grant - Materials and Synthesis Call for proposal ERC-2011-StG_20101014 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator TECHNISCHE UNIVERSITEIT EINDHOVEN Address Groene loper 3 5612 AE Eindhoven Netherlands See on map Region Zuid-Nederland Noord-Brabant Zuidoost-Noord-Brabant Activity type Higher or Secondary Education Establishments Administrative Contact Rob Debeij (Mr.) Principal investigator Maarten Merkx (Dr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all TECHNISCHE UNIVERSITEIT EINDHOVEN Netherlands EU contribution € 1 999 883,00 Address Groene loper 3 5612 AE Eindhoven See on map Region Zuid-Nederland Noord-Brabant Zuidoost-Noord-Brabant Activity type Higher or Secondary Education Establishments Administrative Contact Rob Debeij (Mr.) Principal investigator Maarten Merkx (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
