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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.

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

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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