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Decoding the Epigenomic Regulatory Code by the Use of Single Cell Technologies

Objective

Chromatin regulators adjust genome functions by modifying chromatin states. Comprehensive characterization of chromatin states, associations of chromatin regulators, and expression profiles is crucial for investigating: 1.Cellular differentiation triggers. 2.The nature of the underlying chromatin regulatory mechanisms. 3.The effect of cellular heterogeneity, and 4. How chromatin affects mRNA expression. Mapping chromatin states by sequencing immunoprecipitated chromatin (ChIP-seq) provides an extraordinary resource for studying cellular states. However, a major shortcoming is that the profiles reflect a composite average over the studied cell population, concealing important information about the underlying subpopulations. To address this hurdle, I pioneered Drop-Seq, a novel drop based microfluidic technology for single cell ChIP-seq and RNA-seq. Applying the technique to thousands of embryonic stem (ES) cells, we identified a spectrum of sub-populations defined by differences in chromatin signatures of pluripotency and differentiation priming. However, despite initial progress, the extent and significance of chromatin-state heterogeneity and its relationship with mRNA expression remain largely uncharted. The central aim of this proposal is to develop a novel framework to systematically characterize cell-to-cell variability at the epigenomic level. Our approach will include the development of technology enabling ChIP-seq and RNA-seq on the same cell. We will also exploit drop-based microfluidics to develop a robust CRISPR/Cas9-based approach to assess single and multiple perturbations. Finally, we will apply these innovative technologies to questions about cellular heterogeneity and epigenomic regulation during early differentiation of ES cells. This proposal will reveal the function and interplay between chromatin regulators, histone marks and transcription events, and shed light on the underlying regulation leading to cell fate decisions.

Fields of science (EuroSciVoc)

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Keywords

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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

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

(opens in new window) ERC-2016-STG

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Host institution

THE HEBREW UNIVERSITY OF JERUSALEM
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
EDMOND J SAFRA CAMPUS GIVAT RAM
91904 JERUSALEM
Israel

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Activity type
Higher or Secondary Education Establishments
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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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