Project description
Controlling migration across the body's internal borders to treat disease
The cells and tissues in the body act like little countries defending their borders, carefully controlling what goes in and out as an integral part of homeostasis and signalling. They can also coordinate activities. Among the allies in these functionally relevant synergies are blood and lymphatic vessels, critical for managing fluid flow. When the collaboration breaks down, it can lead to fluid build-up, chronic inflammation and even neurological and cardiovascular disease. BreakingBarriers is studying molecules that modulate the barriers in these two systems both in health and disease. Insight could provide novel ways to treat numerous diseases and conditions ranging from enhanced drug delivery to the brain to lowering lipid uptake to combat obesity.
Objective
Tissue homeostasis requires coordinated barrier function in blood and lymphatic vessels. Opening of junctions between endothelial cells (ECs) lining blood vessels leads to tissue fluid accumulation that is drained by lymphatic vessels. A pathological increase in blood vessel permeability or lack or malfunction of lymphatic vessels leads to edema and associated defects in macromolecule and immune cell clearance. Unbalanced barrier function between blood and lymphatic vessels contributes to neurodegeneration, chronic inflammation, and cardiovascular disease. In this proposal, we seek to gain mechanistic understanding into coordination of barrier function between blood and lymphatic vessels, how this process is altered in disease models and how it can be manipulated for therapeutic purposes. We will focus on two critical barriers with diametrically opposing functions, the blood-brain barrier (BBB) and the lymphatic capillary barrier (LCB). ECs of the BBB form very tight junctions that restrict paracellular access to the brain. In contrast, open junctions of the LCB ensure uptake of extravasated fluid, macromolecules and immune cells, as well as lipid in the gut. We have identified novel effectors of BBB and LCB junctions and will determine their role in adult homeostasis and in disease models. Mouse genetic gain and loss of function approaches in combination with histological, ultrastructural, functional and molecular analysis will determine mechanisms underlying formation of tissue specific EC barriers. Deliverables include in vivo validated targets that could be used for i) opening the BBB on demand for drug delivery into the brain, and ii) to lower plasma lipid uptake via interfering with the LCB, with implications for prevention of obesity, cardiovascular disease and inflammation. These pioneering studies promise to open up new opportunities for research and treatment of neurovascular and cardiovascular disease.
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 neurobiology
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences basic medicine physiology homeostasis
- medical and health sciences health sciences nutrition obesity
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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.
-
H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
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-ADG - Advanced Grant
See all projects funded under this funding scheme
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-2018-ADG
See all projects funded under this callHost institution
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.
75654 PARIS
France
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.