Project description
Understanding nuclear pore structures and lipid metabolism
The nuclear pore complex (NPC) is vital in eukaryotic cells, functioning as a selective transport channel and remodelling the nuclear envelope. Its mechanisms are not well understood, posing key challenges in elucidating NPC protein structures and lipid chemistry, which are crucial for pore formation. The ERC-funded NPC-MEM project will investigate the relationship between nucleoporins, lipids, and lipid metabolism through biochemical reconstitution and system-wide approaches. It will reconstitute and structurally characterise the largest nuclear pore complex (NPC) assembly on a membrane, revealing how NPC assembly drives membrane remodelling and the principles of pore formation. Additionally, the project will identify lipid metabolism enzymes at the inner nuclear membrane (INM) and catalogue all INM lipids.
Objective
The nuclear pore complex (NPC) is a defining component of eukaryotic cells. Its role as a selective transport channel is well-documented, but NPCs also remodel the nuclear envelope, bending and fusing the inner and outer nuclear membranes to form a pore without rupturing the cell nucleus. The underlying mechanism of this process is poorly understood, despite its profound implications for cellular function. My proposal addresses how nuclear pore complexes function as membrane remodelling machines, which remains a fundamental question in eukaryotic biology. Despite its significance, this question has been scarcely explored, primarily due to technical challenges. These include the need for detailed knowledge of NPC protein structure, which has only recently emerged, the lack of tools for NPC membrane biochemistry, and the requirement for a deeper understanding of the inner nuclear membrane (INM), where NPC biogenesis begins during interphase. The process by which NPCs sculpt membrane pores is tied to lipid chemistry, which is the output of lipid metabolism. Therefore, the core strategy of this proposal is to study the nexus between nucleoporins, lipids, and lipid metabolism in an integrated manner, through biochemical reconstitution and system-wide approaches. Using newly developed tools, we will reconstitute and structurally characterize the largest NPC assembly on a membrane to date, revealing how stepwise NPC assembly drives progressive membrane remodelling. This will enable us to reveal the principles of pore membrane formation. Concurrently, we will identify every lipid metabolism enzyme at the INM and use new technology to catalogue all INM lipids. This will provide a foundational reference for nuclear envelope biology and enable us to test how specific lipids impact NPCs and the cell nucleus. This proposal aims to offer pioneering insights into NPC biogenesis and how nuclear lipid metabolism affects NPC function.
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 lipids
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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)
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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.
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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.
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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-ADG
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1090 Wien
Austria
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