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Balancing Act: Understanding metabolic regulation via the acetyltransferase MOF during Drosophila embryogenesis

Project description

Revealing the mechanisms of metabolic regulation during early development

Inherited metabolic disorders are influenced by the maternal environment and passed down to offspring through epigenetic modifications. One crucial epigenetic modification is the MOF-mediated acetylation of histone, which is well documented in Drosophila (fruit fly) and known to be transmitted from mother to embryo. Since embryonic metabolism is temporally coordinated during development, the role of MOF-mediated epigenetic regulation in embryonic metabolism is relatively unexplored. Supported by the Marie Skłodowska-Curie Actions programme, the MetaMOF project aims to address this knowledge gap by exploring the maternal and zygotic contributions of MOF in metabolic regulation during Drosophila embryogenesis. The research will provide insights into underlying mechanisms of metabolic regulation during early development, with wider implications for developmental biology and disease.

Objective

The risk of prenatal onset of metabolic disorders is influenced by the maternal environment, which is inherited by the offspring through epigenetic modifications. Epigenetic modifications utilize metabolic substrates, highlighting the connection between epigenetics and metabolism. In Drosophila, one key epigenetic modification is the MOF-mediated acetylation of histone H4 at lysine 16 (H4K16ac), which is known to be intergenerationally transmitted from mother to embryo. This makes Drosophila an ideal model to study how maternally contributed epigenetic modifications and metabolites shape embryonic development.

MOF operates in two modes: maternal pools establish chromatin accessibility, while zygotic pools facilitate future gene activation. Given that embryonic metabolism is temporally coordinated during development, the role of epigenetic regulation in embryonic metabolism remains unexplored. To address this, I plan to investigate the temporal contributions of MOF in metabolic regulation during Drosophila embryogenesis. Specifically, the following aims will be undertaken:
Aim 1: Understand the maternal contributions of MOF-mediated metabolic regulation.
Aim 2: Investigate the zygotic contributions of MOF in metabolic regulation.
Aim 3: Uncover the association of MOF with the MSL or NSL complex to provide a mechanistic basis for metabolic regulation.

These aims will be achieved through a combination of cutting-edge techniques involving metabolomics, RNA-sequencing, and epigenomics. This research will provide insights into metabolic regulation during early development and its implications for maternal impacts on offspring metabolism. The findings will enhance our understanding of the fundamental mechanisms underlying the epigenetic basis of metabolic regulation, with broader implications for developmental biology and disease.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution
€ 217 965,12
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany
Region
Berlin Berlin Berlin
Activity type
Research Organisations
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Total cost
No data