Project description
Nucleus quality control: the role of nuclear pore complexes
The transport of molecules between the nucleus and the cytoplasm is regulated through large protein structures embedded in the nuclear envelope known as nuclear pore complexes (NPCs). Selective transport through NPCs is crucial for maintaining cellular function and regulating gene expression, DNA replication, and RNA processing. With the support of the Marie Skłodowska-Curie Actions programme, the QualityNPC project aims to investigate a recently identified autophagy pathway in yeast that involves damaged NPC degradation. Researchers will study how this process works by identifying the proteins involved and understanding what triggers it. Project findings will improve our understanding of how cells maintain NPC function with potential implications for human health and disease.
Objective
The nucleus, surrounded by the nuclear envelope (NE), houses genetic material, and nuclear pore complexes (NPCs) mediate the selective passage of molecules between the nucleus and the cytoplasm. NPCs are critical for cellular functions such as protein synthesis and cell division. Dysfunction of NPCs is associated with ageing and disease, highlighting the importance of quality control mechanisms such as NPC degradation. However, the pathways that control NPC degradation remain largely uncharacterized.
A recent study in yeast revealed for the first time a selective autophagy pathway responsible for the degradation of fully assembled NPCs embedded in the NE. NE-derived NPC-containing vesicles are engulfed by an autophagosome through the initial binding of Atg8 to the cytoplasmic-facing Nup159. Although Nup159 is present in all NPCs, NPC degradation occurs rarely under normal conditions and is only upregulated under stress conditions such as starvation, indicating a tightly regulated process.
This research, using Saccharomyces cerevisiae as a model, aims to uncover the machinery and triggers that regulate autophagic NPC degradation through two main objectives. First, to identify the machinery required for the formation of NPC-containing vesicles, using a powerful combination of genome-wide screening and structural insights from cryo-electron tomography. Second, to determine the mechanisms that trigger the formation of NPC-containing vesicles, focusing on two likely triggers: NPC clustering and nuclear content.
The results of this study will redefine our knowledge of NPC quality control and the autophagic degradation pathway for NPCs. The knowledge gained from processes in yeast can potentially be extended to human cell biology, where NPC integrity is crucial in ageing 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 cell biology
- natural sciences physical sciences optics microscopy electron microscopy
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2024-PF-01
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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.