Project description DEENESFRITPL Developing de novo proteins for bone regeneration The successful regeneration of bone tissue to replace areas of bone loss remains a considerable clinical challenge. Efforts are concentrated on designing biomaterials using biomimetic strategies that use proteins from the extracellular matrix. Some of these proteins contain domains capable of binding growth factors, as in the case of the heparin binding II (HBII) domain of fibronectin that can bind bone morphogenetic proteins (BMPs). BMP-2 is a potent osteoinductive molecule. However, HBII lacks specificity for BMP-2. The EU-funded ENGAGE project will identify the hotspot sequences involved in HBII BMP-2 interaction and develop de novo proteins with high affinity to BMP-2 to further exploit them in hydrogel biomaterials to increase bone regeneration. Show the project objective Hide the project objective Objective The successful regeneration of bone tissue to replace areas of bone loss in large defects remains a significant clinical challenge. Efforts have concentrated in the design of biomaterials using biomimetic strategies based on installing bioactivity at their surface using proteins from the extracellular matrix (ECM). Some of these ECM proteins contain domains capable of binding growth factors (GFs). This is the case of the Heparin Binding II (HBII) domain of fibronectin, which has the capacity to bind Bone Morphogenetic Proteins (BMPs). Among them, BMP-2 is known to be a potent osteoinductive molecule. However, the lack of specificity of HBII for BMP-2 limits its application. ENGAGE project aims to identify the hotspot sequences involved HBII-BMP-2 interaction and develop de novo proteins with high affinity to BMP-2 to further exploit them in hydrogel biomaterials for enhancing bone regeneration. To this end, HBII-BMP-2 will be co-crystallized to identify the sequences involved in the interaction. Based on these sequences, de novo mini-binders will be designed using Rosetta computational methodologies and optimized to have high-affinity to BMP-2. The osteoinductive capacity of the selected molecules will be analyzed and the optimal candidates will be used to functionalize hydrogel substrates. In this way, ENGAGE will open the possibility to obtain hydrogels able to sequester specific GFs from the extracellular fluids, avoiding the use of exogenous growth factors and their undesired side effects.The candidate will be trained in new computational and lab skills for protein design under the supervision of a world leader in de novo protein design. These methodologies will be transferred to the Spanish research community for developing novel proteins for biomedical applications. In addition, the obtained skills in paper and project writing, management and leadership will have a strong impact in his competitiveness and the possibility to become an independent scientist. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsengineering and technologyindustrial biotechnologybiomaterialsnatural sciencescomputer and information sciencesartificial intelligencecomputational intelligence Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF-GF - Global Fellowships Coordinator UNIVERSITAT POLITECNICA DE CATALUNYA Net EU contribution € 175 099,20 Address Calle jordi girona 31 08034 Barcelona Spain See on map Region Este Cataluña Barcelona Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Partners (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all Partner Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement. UNIVERSITY OF WASHINGTON United States Net EU contribution € 0,00 Address Brooklyn avenue ne 4333 98195 9472 Seattle wa See on map Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 88 632,96
