Project description
A zebrafish model of the blood–brain barrier
The blood–brain barrier (BBB) is paramount for brain homeostasis since it defines the molecular and cellular transit between the brain and the circulatory system. This is achieved through complex communications between endothelial cells and other components of the neurovascular system. To study BBB permeability, the EU-funded Ctrl-BBB project will employ the zebrafish as a model because of its transparent nature and its capacity to undergo non-invasive genetic analyses. Considering that the BBB prohibits drug delivery into the CNS, understanding how it is regulated will unveil novel therapeutic avenues for various disorders including stroke, multiple sclerosis and neurodegeneration.
Objective
Brain endothelial cells (ECs) are endowed with a set of molecular and metabolic adaptations that stringently orchestrate the molecular and cellular transit between the brain and the circulatory system. These adaptations constitute the blood-brain barrier (BBB) and are pivotal to brain homeostasis and protection. Accordingly, BBB dysfunction is a unifying hallmark of many cerebrovascular diseases, including stroke, multiple sclerosis and neurodegeneration. Healing the BBB to treat to the brain is therefore emerging as a powerful therapeutic avenue for a spectrum of human CNS disorders. In addition, through its neuroprotective function, the BBB represents the main obstacle for CNS drug delivery. There is consequently an urgent need to identify methods to control BBB in health and disease. Of pivotal importance, BBB is not genetically hardwired, but instead results from ongoing neurovascular communications taking place between the ECs and the other components of the neurovascular unit. Shedding light on these communications, and raising our understanding to the mechanistic level will undoubtedly yield transformative therapeutic strategies for human brain disorders. A key obstacle in the study of BBB permeability resides in its complex regulation across cells and tissues. This complexity cannot be recapitulated in cell culture experiments. Our laboratory has recently identified and validated the transparent zebrafish as ideally suited to facilitate these studies, by empowering non-invasive genetic analyses of BBB function under normoxia. Together with a conserved BBB genetic instruction program, the zebrafish cerebrovasculature qualifies as a an alternative “miniature BBB model” where neurovascular communication can be studied at an unprecedented pace. Ctrl-BBB will pioneer synergistic approaches between the zebrafish and the mouse model, to bring BBB research in the era of highly parallel genetic approaches and BBB-focused therapeutic strategies for brain disorders.
Fields of science (EuroSciVoc)
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This project's classification has been validated by the project's team.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
This project's classification has been validated by the project's team.
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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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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-COG - Consolidator Grant
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2019-COG
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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.
1050 Bruxelles / Brussel
Belgium
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