Objective
MAIN GOAL: To characterize the role of peroxisomal fatty acid oxidation (pFAO) and its relative importance in the differently active endothelial cell (EC) subtypes during blood vessel sprouting (angiogenesis).
BACKGROUND & RATIONALE: Activation of ECs by growth factors such as VEGF induces vessel sprouting, requiring a switch from quiescent phalanx ECs to a leading tip EC and proliferating stalk ECs. The host lab recently showed that this angiogenic switch requires a metabolic switch, with specific roles for glycolysis and mitochondrial fatty acid oxidation (FAO). ECs also have peroxisomes, which metabolize very long chain fatty acids (VLCFAs), but nothing is known about the possible role of peroxisomes/pFAO in ECs. Multifunctional protein 2 (MFP2) is the key enzyme of pFAO. Initial data from the host lab indicates that MFP2 silencing in ECs impairs vessel sprouting in vitro. I hypothesize that pFAO regulates the tip/stalk/phalanx EC subtypes differently during sprouting and will examine the underlying (peroxisomal) metabolic mechanisms.
METHODOLOGY: I will use a multidisciplinary approach, combining molecular and cellular biology, in vitro and in vivo angiogenesis models, and conditional mouse genetics, to characterize the role of MFP2 in vascular sprouting. I will use scRNA-seq to define the (peroxisomal) metabolic gene signature of the 3 EC subtypes and explore whether MFP2 loss results in population shifts of tip, stalk and phalanx ECs. Furthermore, I will use state-of-the-art metabolomics and 13C tracing to define the metabolic fate of peroxisomally metabolized VLCFAs, with the ultimate goal of evaluating their physiological relevance in ECs.
NOVELTY AND TRANSLATIONAL IMPACT: The data promise first insights in pFAO’s role in vessel sprouting and the first (peroxisomal) metabolic gene signature of tip, stalk & phalanx EC subtypes at single cell level, and may identify pFAO genes as potential novel targets in strategies to inhibit pathological angiogenesis.
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 genetics
- natural sciences chemical sciences electrochemistry electrolysis
- natural sciences biological sciences biochemistry biomolecules lipids
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.1.3. - 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-EF-ST - Standard EF
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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-2017
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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.
9052 ZWIJNAARDE - GENT
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.