Objective
How the genome controls precise, cell-type specific gene expression is crucial for cell identity and differentiation. Short cis-regulatory elements, such as enhancers, are distributed in extended regulatory domains surrounding their target gene, which in mammals typically span hundreds of kilobases. Although all evidence indicates that gene regulation is controlled by the combined action of large domains, our current understanding mostly focuses on enhancers. If and how intervening DNA sequences, enhancer order, or spacing within regulatory domains contribute to gene regulation is unknown. The reason for this largely unexplored aspect lies in our limited ability to systematically alter large genomic regions.
In this study, we will use recent advances in synthetic biology to overcome this limitation. From synthetic DNA, we will create variants of entire gene regulatory domains and integrate these into mouse embryonic stem cells. We will test synthetic regulatory domain function in tailored gene expression analyses using cell culture, organoid, and in vivo models. By investigating regulatory elements with respect to their surrounding regulatory domain, we will uncover hidden rules of gene regulation.
In variant regulatory domains we will systematically assay understudied parameters, such as enhancer spacing, order, or inter-enhancer sequences. We will use single-molecule methods to measure gene expression level; use organoid and in vivo systems to profile cell-type specific changes in expression patterns, and we will use the unique potential of synthetic DNA to understand the fundamental link between DNA sequence and chromatin composition of regulatory domains. With this interdisciplinary approach, we aim to uncover previously hidden layers of genomic information. The insights generated from this work will provide a novel and unique view on the organization of the non-coding genome, with the potential to expand our ability to read and write genomic DNA sequences.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences zoology mammalogy
- natural sciences biological sciences genetics genomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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.
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.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-STG
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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.
10117 Berlin
Germany
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.