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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.

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

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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