Objectif 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. Champ scientifique natural 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) Thème(s) ERC-SG-PE5 - ERC Starting Grant - Materials and Synthesis Appel à propositions ERC-2011-StG_20101014 Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil TECHNISCHE UNIVERSITEIT EINDHOVEN Contribution de l’UE € 1 999 883,00 Adresse GROENE LOPER 3 5612 AE Eindhoven Pays-Bas Voir sur la carte Région Zuid-Nederland Noord-Brabant Zuidoost-Noord-Brabant Type d’activité Higher or Secondary Education Establishments Contact administratif Rob Debeij (Mr.) Chercheur principal Maarten Merkx (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire TECHNISCHE UNIVERSITEIT EINDHOVEN Pays-Bas Contribution de l’UE € 1 999 883,00 Adresse GROENE LOPER 3 5612 AE Eindhoven Voir sur la carte Région Zuid-Nederland Noord-Brabant Zuidoost-Noord-Brabant Type d’activité Higher or Secondary Education Establishments Contact administratif Rob Debeij (Mr.) Chercheur principal Maarten Merkx (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
