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Single-cell epigenomics: quantifying epigenetic changes in individual cells using DamID

Objective

Phenotypic variation arises from the heritable acquisition of cell-type specific gene-expression programs. Key in understanding cellular specification is to elucidate the epigenetic mechanism that underlies transcriptional heterogeneity. Thus a central question in biology is how cell-to-cell variability in the epigenome contributes to the emergence of phenotypic differences. However, current techniques to profile the epigenome require populations of cells and consequently present ensemble averages of the underlying biology. Therefore, to grasp the molecular concept behind the cellular acquisition of heritable traits it is essential to develop techniques to profile the epigenome at the single-cell level.
The advent of single-cell genomics enabled profiling of few epigenetic features and transcriptomics in single cells; however, this toolbox is still very restricted and moreover, to directly correlate the variability in the epigenome to changes in gene-expression activity it is pivotal to device methods to obtain both measurements from the same cell. Therefore, to bridge these shortcomings in the epigenetic toolbox, we plan to develop and apply novel techniques to profile the epigenome in single cells. With this proposal we aim to (1) develop a method to map histone modifications in single cells (2) develop a method to map chromatin organization in single cells (3) develop a method to obtain combined measurements of the epigenome and the transcriptome of the same cell (4) apply these and previously developed single-cell methods, to different biological systems to study how the epigenome contributes to lineage specification. Collectively, the goal of this proposal is to develop a comprehensive single-cell toolbox to take the field to the next (epigenomic) level and to work towards elucidating the molecular mechanism behind cellular specification.

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.

ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2015-STG

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Host institution

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
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.

€ 1 500 000,00
Address
KLOVENIERSBURGWAL 29 HET TRIPPENHUIS
1011 JV AMSTERDAM
Netherlands

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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.

€ 1 500 000,00

Beneficiaries (1)

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