Objective
The formation of a functional patterned vascular network is essential for development, tissue growth and organ physiology. Several human vascular disorders arise from the mis-patterning of blood vessels, such as arteriovenous malformations, aneurysms and diabetic retinopathy. Although blood flow is recognised as a stimulus for vascular patterning, very little is known about the molecular mechanisms that regulate endothelial cell behaviour in response to flow and promote vascular patterning.
Recently, we uncovered that endothelial cells migrate extensively in the immature vascular network, and that endothelial cells polarise against the blood flow direction. Here, we put forward the hypothesis that vascular patterning is dependent on the polarisation and migration of endothelial cells against the flow direction, in a continuous flux of cells going from low-shear stress to high-shear stress regions. We will establish new reporter mouse lines to observe and manipulate endothelial polarity in vivo in order to investigate how polarisation and coordination of endothelial cells movements are orchestrated to generate vascular patterning. We will manipulate cell polarity using mouse models to understand the importance of cell polarisation in vascular patterning. Also, using a unique zebrafish line allowing analysis of endothelial cell polarity, we will perform a screen to identify novel regulators of vascular patterning. Finally, we will explore the hypothesis that defective flow-dependent endothelial polarisation underlies arteriovenous malformations using two genetic models.
This integrative approach, based on high-resolution imaging and unique experimental models, will provide a unifying model defining the cellular and molecular principles involved in vascular patterning. Given the physiological relevance of vascular patterning in health and disease, this research plan will set the basis for the development of novel clinical therapies targeting vascular disorders.
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.
- medical and health sciences clinical medicine angiology vascular diseases
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- natural sciences biological sciences cell biology cell polarity
- medical and health sciences basic medicine physiology
- medical and health sciences clinical medicine ophthalmology retinopathy
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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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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.
ERC-STG - Starting Grant
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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) ERC-2015-STG
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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.
1649 028 Lisboa
Portugal
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.