Project description
Decoding intracellular communication
Eukaryotic cells contain membrane-bound organelles which enable them to compartmentalise biochemical and biological processes. The endoplasmic reticulum (ER) serves a vital purpose in facilitating precise inter-organelle communication, supplying proteins and lipids. Funded by the European Research Council, the conNEctoER project addresses a gap in scientific knowledge related to the mechanisms governing ER-nuclear envelope (NE) junctions. Recent findings suggest a dynamic ultrastructure of these junctions during the cell cycle, prompting investigation into the role of membrane proteins. By combining electron microscopy and live imaging, researchers aim to elucidate the ER-NE junction formation and function, shedding light on gene expression, nuclear organisation, and disease mechanisms.
Objective
Compartmentalization into membrane-bound organelles is a key feature of all eukaryotic cells, and communication between organelles needs to be tightly controlled. A key organelle for the inter-organelle communication is the endoplasmic reticulum (ER), which is the major site of lipid and membrane protein synthesis. The ER exchanges molecules by forming stable contact sites with multiple organelles such as mitochondria via specific tethering proteins and transporters. In contrast to these contact sites, the ER is linked to the nucleus via direct fusion to the outer nuclear membrane of the nuclear envelope (NE). These ER-NE junctions are essential for supplying the lipids and proteins that are synthesized in the ER to the NE. Hence, nuclear function and morphology depend on the proper communication via ER-NE junctions. However, the biogenesis, architecture and maintenance of ER-NE junctions have remained elusive.
We have recently found that ER-NE junctions exhibit a narrow and constricted ultrastructure during the cell cycle in mammalian cells. These observations led us to postulate that ER-NE junctions are formed and maintained by specific membrane-shaping proteins that are crucial for nuclear function. Here, we propose to identify the molecular mechanism that governs the structure and function of ER-NE junctions. We will provide a quantitative and dynamic high-resolution view of these enigmatic structures by combining time-resolved electron microscopy and quantitative live imaging with molecular perturbations. Using these datasets, we aim to develop a mechanistic model of how ER-NE junctions form and contribute to nuclear function.
The NE proteins supplied via ER-NE junctions have critical roles in gene expression, nuclear organization, and nuclear pore biogenesis, as well as in differentiation, development, and disease. Therefore, our research will provide a new conceptual framework that will open lines of investigation in many fields beyond ER/NE biology.
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
- natural sciences physical sciences optics microscopy electron microscopy
- natural sciences biological sciences biochemistry biomolecules lipids
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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.
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-2023-COG
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1090 WIEN
Austria
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