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PerMet SIGNED

Role of peroxisomal fatty acid β-oxidation in vessel sprouting

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 PerMet project word cloud

Explore the words cloud of the PerMet project. It provides you a very rough idea of what is the project "PerMet" about.

angiogenic    physiological    regulates    indicates    host    vivo    mechanisms    chain    relevance    explore    metabolomics    background    combining    induces    vitro    shifts    subtypes    rationale    relative    quiescent    nothing    seq    signature    insights    fate    single    switch    showed    first    ultimate    ecs    protein    models    novelty    differently    population    vessel    endothelial    metabolize    acids    molecular    pfao    biology    pathological    stalk    metabolic    activation    mitochondrial    metabolized    lab    inhibit    mouse    hypothesize    cellular    genes    impairs    peroxisomally    oxidation    promise    angiogenesis    methodology    silencing    examine    glycolysis    multidisciplinary    acid    initial    vascular    fao    vegf    tip    tracing    genetics    active    conditional    peroxisomal    gene    strategies    13c    proliferating    ec    requiring    enzyme    underlying    scrna    data    translational    fatty    peroxisomes    multifunctional    phalanx    main    vlcfas    mfp2    blood    cell    roles    sprouting   

Project "PerMet" data sheet

The following table provides information about the project.

Coordinator
VIB VZW 

Organization address
address: RIJVISSCHESTRAAT 120
city: ZWIJNAARDE - GENT
postcode: 9052
website: www.vib.be

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Belgium [BE]
 Total cost 160˙800 €
 EC max contribution 160˙800 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2017
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2018
 Duration (year-month-day) from 2018-04-01   to  2020-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    VIB VZW BE (ZWIJNAARDE - GENT) coordinator 160˙800.00

Map

 Project 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.

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The information about "PERMET" are provided by the European Opendata Portal: CORDIS opendata.

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