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Propagating DNA Modifications Across the Cell Cycle

Objective

Background
DNA hydroxymethylation and methylation are marks on DNA that help define cell identity and maintain genome stability. DNA hydroxymethylation is recently discovered, and the mechanisms underlying its maintenance are uncharacterised. DNA methylation is crucial for cell function, but large blocks of DNA lose methylation in cancerous and ageing cells. It has been speculated that this is due to aberrant maintenance during cell division, however, technical limitations have prevented this from being directly assessed. By developing a novel technology to study maintenance of these marks, I will test this hypothesis for the first time.
Approach
This new technology will track how DNA methylation and hydroxymethylation patterns are restored after DNA replication, using both mass-spectrometry and genomics. Using this, I will track restoration of these marks following DNA replication, and test whether DNA methylation loss is caused by cell cycle speed, depleted methionine levels late in replication, or a combination of both. This will be followed up by functional analyses of key maintenance DNA hydroxymethylation and methylation factors. Thus, this work combines my past experience in DNA methylation with the host lab’s expertise in chromatin dynamics during DNA replication.
Impact
This will be the first quantitative study of how patterns of DNA methylation and DNA hydroxymethylation are propagated between cell divisions, which is essential to their roles in defining and maintaining cell identity. The results will bring seminal and novel understanding of these marks from both basic and biomedical perspectives, by elucidating how epigenome maintenance is linked to both DNA replication and the epigenetic changes seen in disease. By dissecting in unprecedented resolution the mechanisms underlying propagation of DNA methylation and hydroxymethylation, this work will unveil the basis for epigenetic inheritance of these marks between cell generations.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2016

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Coordinator

KOBENHAVNS UNIVERSITET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 212 194,80
Address
NORREGADE 10
1165 KOBENHAVN
Denmark

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Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 212 194,80
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