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M-DrivE TERMINATED

Metabolic Drivers of Epigenetic Modifications: metabolic inducers of histone post-translational modifications in a biological setting

Total Cost €

0

EC-Contrib. €

0

Partnership

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 M-DrivE project word cloud

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

intracellular    ppt    unexplored    inducing    influence    epigenetic    coa    expression    metabolically    combining    donor    expertise    synthesis    upregulate    probe    cellular    previously    permeable    acetyl    affording    coenzyme    protein    appropriate    interplay    tolerated    precursor    histone    post    interactions    sekirnik    natural    acyl    acetylation    translational    proteins    electrostatically    highlighting    substrates    disorder    position    organism    genetic    model    induction    endogenous    metabolic    backgrounds    form    units    rare    places    sole    epigenetics    species    add    substrate    illuminate    phosphopantetheine    faulty    dr    advantage    shown    cell    synthesising    prolific    storage    implication    enzymes    dna    first    derivatives    diverse    efficient    bypassing    progress    international    enrichment    characterised    exploited    enzyme    chemical    metabolomics    serum    vehicle    lack    modification    metabolism    route    rapid    gene    acylations    realise    complementarity    tools    partnership    biochemical    subsequent    doses    modifications    bio    demonstration    demonstrating    remove    acies    therapeutic    function    recognise    native    stable   

Project "M-DrivE" data sheet

The following table provides information about the project.

Coordinator
ACIES BIO BIOTEHNOLOSKE RAZISKAVE IN RAZVOJ DOO 

Organization address
address: TEHNOLOSKI PARK 21
city: LJUBLJANA
postcode: 1000
website: www.aciesbio.com

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 Slovenia [SI]
 Total cost 157˙287 €
 EC max contribution 157˙287 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-SE
 Starting year 2018
 Duration (year-month-day) from 2018-05-01   to  2020-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    ACIES BIO BIOTEHNOLOSKE RAZISKAVE IN RAZVOJ DOO SI (LJUBLJANA) coordinator 157˙287.00

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 Project objective

Post-translational chemical modifications to histone proteins – the storage units of DNA – influence gene expression electrostatically and through specific protein-protein interactions, the study of which is known as epigenetics. Although many enzymes have been identified which add, remove or recognise these modifications, the implication of metabolism in the induction of epigenetic states is a recent development – particularly highlighting acetyl coenzyme A (CoA) as the sole donor for acetylation. Due to the lack of appropriate biochemical tools, this emerging field has not yet been exploited, however Acies Bio’s leading work on the efficient synthesis of 4’ phosphopantetheine (4-PPT), a natural precursor of the prolific substrate CoA, places us in a unique position to realise the novel approach of metabolically inducing epigenetic modifications. In progress towards therapeutic use bypassing faulty metabolism in a rare genetic disorder, we have shown that 4-PPT is cell permeable, serum-stable, tolerated at high doses without side-effects, and can also upregulate histone acetylation. This presents a previously unexplored route to develop 4-PPT as a novel vehicle for the delivery of diverse intracellular acyl-CoA species, and subsequent histone modification. Taking advantage of the interplay between metabolic and epigenetic states, and the complementarity of backgrounds that Acies Bio and Dr Sekirnik can provide through an international partnership combining expertise in both fields, our proposed work would illuminate recently characterised histone acylations. By synthesising novel 4-PPT derivatives, and demonstrating their activity on a cellular and model organism level, we will develop new tools to enable rapid enrichment of rare endogenous modifications to probe their function. This would form the first demonstration of use of native enzyme substrates to affect epigenetic states, affording new European research opportunities in both metabolomics and epigenetics.

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