Project description
Delineating the mechanisms responsible for the tissue-specific nature of endothelial cells
Endothelial cells (ECs) line blood and lymphatic vessels forming a barrier between blood and tissues. They are highly heterogeneous and acquire organ-specific signatures to serve tissue needs. The EU-funded ECSiTe project aims to investigate the tissue-specific mechanical, biochemical and genetic factors responsible for the different EC signatures. Researchers will set up an artificial in vitro EC model that can recapitulate different tissue conditions in terms of mechanical forces and biochemical triggers. They will determine the mechanism by which ECs integrate different signals to alter their phenotype, opening new possibilities for tissue engineering and vascular repair.
Objective
Endothelial cells (ECs) specialize towards tissue-specific needs by shaping their phenotypes in response to microenvironmental stimuli, becoming a highly heterogeneous population. Overlooking the EC heterogenic nature most likely underlies the low efficacy and side-effects of broad-spectrum treatments for vascular bed-specific diseases. However, little is known on the interplay between the factors regulating the EC signatures, and tissue engineering research has essentially used standard and poorly differentiated ECs. The objective of this proposal is to investigate the mechanisms by which tissue-specific mechanical, biochemical and genetic factors interact to regulate EC signatures. To do so, brain and aortic valve ECs –non-standard and highly specialized EC types– will be used. First, by using custom-made hydrogels and a flow chamber device, a combination of different levels of tissue stiffness and shear stress will be applied to ECs in culture. The impact and interaction of both mechanical forces on EC features will be determined by analysing changes in EC phenotypes and in gene expression profiles. Then, brain and valve-specific mechanical forces will be selected, and brain and valve ECs will be cultured under organ-matching mechanical forces but under organ-switched biochemical factors. Because these ECs have strong signatures, by analysing phenotypical shifts, the impact of tissue-specific biochemical factors on EC signatures will be determined. Finally, the genetic impact on brain and valve EC phenotypes and the capability of modulating these through microenvironmental design will be studied by analysing phenotypical shifts after culturing brain and valve ECs under organ-switched total (mechanical and biochemical) environments. In a nutshell, this proposal will provide new knowledge in how specialized ECs integrate the different factors regulating their heterogeneity, leading to new future perspectives on tissue-specific vascular bed repair strategies.
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.
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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-2020
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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.
3000 Leuven
Belgium
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.