Objective
Shape and function of the vertebrate nucleus depend on the choreographed interplay between lipids, proteins, and DNA to form the nuclear envelope. Even small molecular changes, such as point mutations in the proteins of the nuclear envelope (the lamina) cause detrimental human diseases including premature aging, cancer, and heart disease. To date, a clear, mechanistically compelling explanation for the dynamic coupling of lipids, proteins, and DNA to safeguard nuclear shape and function is still missing. We here propose to build minimal, synthetic nuclei (‘Organelloids’) bottom-up as a tool to study the self-assembly of a functional nucleus.
We recently discovered the conserved molecular machinery that ensures the assembly of the nuclear envelope in open vertebrate mitosis. Our data point to uncharacterized fundamental mechanisms that couple the fusion of lipid-membrane sheets into a continues nuclear membrane to the formation of the lamina, and the organization of chromatin in the same chain of events.
In this proposal, we will leverage our recent advances in reconstitution to build ‘Organelloids’ to recapitulate shape and function of the membrane-lamina-chromatin confluence. Using these nuclear Organelloids we will resolve the nuclear assembly process in high resolution by applying integrated structural biology and determine the unknown biophysical principles that drive the self-organization of individual molecules into one functional organelle. Our strategy will reveal the unknown hierarchical relationship between lipids, proteins, and DNA and produce detailed mechanistic models for the formation and coupling of functional subdomains that are commonly observed in the nuclear membrane, the lamina and chromatin. With cell models and top-down approaches we ultimately aim to define the fundamental principles that govern nuclear biogenesis with implications for health and disease.
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 biochemistry biomolecules lipids
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
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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-2023-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.
80539 MUNCHEN
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.