Project description
Chromatin and nuclear architecture
The nucleus is the largest and stiffest organelle in the cell, largely responsible for determining the mechanical properties of the cell. The nucleus contains DNA, which is tightly packed into chromatin and then further folded into higher structures. Perturbation of this architecture, as seen in metastatic cancers, is associated with aberrant gene expression and altered cellular behaviour. The ERC-funded RNOME project aims to overcome current technical challenges by developing tools to visualise chromatin folding in real time inside living cells. The key objective is to elucidate the role of chromatin in shaping nuclear architecture and cellular phenotypes. This information will help scientists establish a predictive, multiscale model for future epigenetic therapeutic strategies.
Objective
The content of the cell nucleus is highly organized at different levels. Chromatin is partitioned into domains that carry different post-translational histone modifications, and it exhibits a multiscale structural organization from small loops to large compartments. Nuclear RNAs and proteins recognize cues on chromatin, forming different types of chromatin-associated complexes and condensates. The nucleus as a whole is the largest and stiffest organelle of the cell and modulates its mechanical properties. Dysregulation of the nucleome at any level goes along with altered gene- and mechano-regulation in diseases such as metastatic cancers. Currently, the functions of the different organizational levels of chromatin, their mutual relationships and the impact on cellular phenotypes are poorly defined.
Progress in this field has been hindered by several technical limitations. One is the inability to study chromatin folding in single living cells, which would allow to interrogate its dynamics, to assess its response to perturbations in real-time, and to relate it to the mechanical properties of the same cell. Another limitation is the lack of tools to selectively reengineer different levels of the nuclear organization to test their function.
With the RENOME project, I propose to overcome these limitations by developing systems to study chromatin compartments in real-time and to reshape different organizational levels of the nucleome in a tunable manner. These tools will make it for the first time possible to define the functional impact of nuclear organization across scales, from single molecules to mammalian cultured cells and 3D organoids.
RENOME links chromatin regulation, phase separation and nuclear mechanobiology, with the goal to connect molecular mechanisms to cellular behavior. By providing a multi-scale predictive model for the organization of the nucleome and a toolbox for its reengineering, it will lay the groundwork for future epigenetic therapies.
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 biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
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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)
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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.
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-COG
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75794 PARIS
France
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