Project description
The folding principles of mitotic chromosomes
Mitosis is the process in which a cell divides to produce two genetically identical daughter cells. During this process, the genome undergoes a striking transformation: from a relaxed chromatin state it gets packaged into mitotic chromosomes. Although this is central for correct chromosome segregation, molecular information on the folding and organisation of mitotic chromosomes is missing. The ERC-funded MITOFOLD project aims to uncover the spatial and temporal mechanisms shaping chromosome architecture during mitosis in human cells. Using advanced molecular tracing and imaging methods, researchers hope to reveal how structural chromosome features emerge and are regulated. The project will provide important knowledge into chromosome organisation in health and disease.
Objective
Mitosis is a fundamental biological process every cell undergoes at least once. It requires a dynamic and dramatic restructuring of the genome from extended interphase chromatin to compact individual mitotic chromosomes capable of faithful segregation. Altered nucleosome interactions, phase separation and loop extrusion have all been proposed to play important roles in shaping mitotic chromosomes. However, what the internal architecture of single mitotic chromosomes is, and how this architecture is established in space and time by different forces inside the cell remains unclear. This lack of knowledge precludes a comprehensive mechanistic understanding of mitotic chromosome folding and unfolding.
This project aims to resolve the folding principles of chromosomes during mitotic compaction and decompaction in situ, in single human cells. To achieve this, we will combine newly developed nanoscale DNA tracing technology with quantitative single protein imaging approaches to achieve a systematic structural analysis of mitotic chromosome folding throughout mitosis. We will investigate when and where which structural features are first established, and then use targeted, acute perturbations to dissect which regulators are required to form and maintain them. The resulting data will provide an in situ structure-based model to explain the essential function of the genome in mitosis and will allow us to understand the spatio-temporal coordination of the underlying molecular and physical mechanisms. Overall, the proposed project will provide a new framework for understanding the physiological and pathological roles of mitotic chromosome restructuring during cell division.
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 biochemistry biomolecules proteins
- 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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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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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.
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-2023-ADG
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69117 Heidelberg
Germany
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