Project description
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.
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 (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- engineering and technology industrial biotechnology biomaterials
- natural sciences computer and information sciences artificial intelligence computational intelligence
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2018
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
08034 BARCELONA
Spain
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.