Objective
Biophysical research over the last two decades has revealed that an impressive number of mechanical signals are key regulators of cell behavior. So far, the focus has been on understanding fundamental mechanosensing and transduction mechanisms in health and disease. As increasing numbers of molecular players and signalling pathways are identified, the time has come to utilize this knowledge for diagnosing and treating diseases where mechanical processes play a role. In this proposal, I aim to target integrins to deliver reporter molecules and drugs to cells with a distinct mechanical phenotype. Integrins are transmembrane receptors through which cells can sense, transmit and discriminate biomechanical forces. During cell adhesion and migration, integrins engage with specific ligands in the extracellular matrix and undergo integrin recycling through continuous endo- and exocytosis. This known endocytic pathway, integrin clustering during adhesion and overexpression in disease states has made integrins a prime target for drug delivery. However, the chemical and physical factors governing integrin-mediated uptake of drugs and their intracellular fate are unknown. I propose to utilize molecular force sensor (MFS) technology to deconvolute the key factors in integrin-mediated drug delivery. Using rational protein design, a series of coiled coil MFSs with distinct chemical (charge and hydrophobicity) and physical (mechanical and thermal stability) properties will be produced. The molecular constructs will be appended with the integrin-targeting RGD motif, a fluorescent protein to investigate the intracellular fate and an actin-binding protein as a model drug that may potentially interfere with the cytoskeleton architecture. This MFS-based drug delivery system will enlighten the pivotal factors of integrin-mediated delivery, provide a diagnostic assay for discriminating cells based on their mechanical phenotype and open up the road towards mechano-targeted drug delivery.
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 electrical engineering, electronic engineering, information engineering electronic engineering sensors
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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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2022-PF-01
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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.
4040 Linz
Austria
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.