Project description
The interconnection between chromosomal topology and transcriptional regulation
Accumulating evidence indicates that mammalian genomes are organised in topologically distinct subdomains which interact with each other and share regulatory landscape. Although disruption of these domains has been associated with disease, little is known whether they are a consequence of transcriptional activity. Scientists of the EU-funded eXcape3D project will use the X chromosome inactivation (XCI) as a model system to identify the regulatory elements implicated in the formation of chromosomal subdomains. The project will provide important insight into genome topology and the role of the non-coding genome in gene regulation.
Objective
Mammalian genomes are structurally organized into sub-chromosomal self-interacting domains called topologically associating domains (TADs). Functionally, genes embedded within the same TAD appear to be co-regulated by their shared regulatory landscapes, suggesting the tendency of the genome to be divided into discrete regulatory domains. Although disrupting TAD boundaries has been shown to result in aberrant patterns of gene expression, whether TAD organisation is cause or consequence of transcriptional activity remains largely unknown, as well as the regulatory elements that direct TAD formation and long-range chromatin interactions within TADs. This project aims to define the exact functional link between genome topology and transcriptional regulation by exploiting the mammalian dosage compensation mechanism X-Chromosome Inactivation (XCI) as a model system. First, I will identify the combination of regulatory elements that allow a subset of X-linked genes to resist the transcriptional silencing of one entire X chromosome in female cells. Then, I will characterise their functional and structural relevance by combining advanced epigenetic tools for the manipulation of complex regulatory networks with transcriptomic analysis and chromosome conformation capture, an innovative method that allows to define the 3D structure of chromosomes within the nucleus. This project represents a unique opportunity to enhance our understanding of genome topology, providing valuable insights into the roles of the non-coding genome in gene regulation. Considering my personal professional background, and the outstanding level of scientific excellence of the host institution, this project promises a great potential of radically advancing the field and, in addition, will provide the European Research Area with a highly-qualified expert scientist who has the technical and complementary skills to successfully lead a European research team.
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 mathematics pure mathematics topology
- natural sciences biological sciences genetics chromosomes
- natural sciences biological sciences genetics genomes
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2018
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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.
69117 Heidelberg
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.