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Histone modifying enzymes as direct regulators of metabolic reprogramming: Towards a New Paradigm

Projektbeschreibung

Wie Epigenetik und Stoffwechsel zusammenhängen

Forschungsergebnisse deuten immer häufiger darauf hin, dass die Epigenetik bei der Regulierung der Genexpression für den Stoffwechsel eine zentrale Rolle spielt. Das Forschungsteam des EU-finanzierten Projekts MetabolACE will nun herausfinden, mit welchen Mechanismen Histon-modifizierende Enzyme auf den Stoffwechsel einwirken. Der Hypothese der Forschenden zufolge verbrauchen diese Enzyme große Mengen lebenswichtiger Stoffwechselprodukte und verändern so deren Masse, was wiederum Umstellungen im Stoffwechsel hervorruft. Mithilfe einer Kombination aus Techniken der Epigenetik und Metabolomik wird das Team untersuchen, wie sich die Aktivität von Histonacetyltransferasen (HAT) auf das vorhandene Acetyl-Co-Enzym A (Acetyl-CoA) in den Zellen auswirkt. Diese Arbeiten werden neues Grundlagenwissen über den Zusammenhang von Epigenetik und Stoffwechsel im gesunden und erkrankten Körper liefern.

Ziel

Accumulating evidence in recent years has highlighted strong regulatory interactions between epigenetic mechanisms and metabolic transformations, mainly through transcriptional control of key metabolic genes. However, what has been overlooked is the direct effect of histone modifying enzymes on cellular metabolism as they are large consumers of sentinel metabolites. Therefore, I hypothesize that histone modifying enzymes and their mediated post-translation modifications (PTMs) on histones directly drive metabolic rewiring which subsequently impacts various cellular processes including gene expression. Specifically, this fellowship will focus on histone acetyltransferases (HATs) that use acetyl coenzyme A (Acetyl-CoA) as their sole substrate. Using interdisciplinary, state-of-the-art approaches that integrate subcellular metabolomics and high-throughput epigenomic techniques I will interrogate how the activity of HATs controls the abundance of acetyl-CoA and, in turn, defines the metabolic status of a cell leading to a subsequent reciprocal effect on the epigenetic landscape and genome regulation. Firm preliminary data, that I have recently generated, support the proposed project hypothesis and demonstrate that the experimental design is credible. During this project, my in-depth knowledge of metabolism and mass spectrometry skills will be combined with the expertise of epigenetics and histone biology that I will acquire at the host lab to reveal a new pathway through which histone PTMs function. This work will unveil a new fundamental link between epigenetics and metabolism and will be the commencing point for important future work in health and disease. Importantly, this fellowship will propel my academic career and help me become a scientific leader at the interface of epigenetics and metabolism since it will act as a stepping stone towards securing new research funding and acquiring a tenure track position.

Wissenschaftliches Gebiet (EuroSciVoc)

Schlüsselbegriffe

Programm/Programme

Thema/Themen

Finanzierungsplan

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

Alle im Rahmen dieses Finanzierungsinstruments finanzierten Projekte anzeigen

Aufforderung zur Vorschlagseinreichung

(öffnet in neuem Fenster) H2020-MSCA-IF-2019

Alle im Rahmen dieser Aufforderung zur Einreichung von Vorschlägen finanzierten Projekte anzeigen

Koordinator

UNIVERSITY OF CYPRUS
Netto-EU-Beitrag
€ 145 941,12
Adresse
AVENUE PANEPISTIMIOU 2109 AGLANTZI
1678 Nicosia
Zypern
Region
Κύπρος Κύπρος Κύπρος
Aktivitätstyp
Higher or Secondary Education Establishments
Links
Gesamtkosten
€ 145 941,12