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Metabolic Drivers of Epigenetic Modifications metabolic inducers of histone pos...

Metabolic Drivers of Epigenetic Modifications metabolic inducers of histone post translational modifications in a biological setting 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.... ver más

30/04/2020

ACIES BIO

157K€

Presupuesto del proyecto: 157K€

Líder del proyecto

ACIES BIO BIOTEHNOLOSKE RAZISKAVE IN RAZVOJ D... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2020-04-30

MSCA-IF-2016: Individual Fellowships

I+D

Cerrada hace 8 años

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1 Participantes

ACIES BIO

157.29K€ | Lider

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Duración del proyecto: 36 meses Fecha Inicio: 2017-04-04
Fecha Fin: 2020-04-30

Líder del proyecto

ACIES BIO BIOTEHNOLOSKE RAZISKAVE IN RAZVOJ D... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 157K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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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