Project description
A new pathway for cellular secretion
Cells degrade unwanted material through a process known as autophagy: this involves membrane vesicles which encapsulate and transport degraded cargo out of the cell. The ERC-funded autoXitus project focuses on a newly discovered cellular process called autoxitus, which functions as an alternative to traditional autophagy by allowing cells to expel large cellular material such as organelles. The study aims to uncover the molecular mechanisms of autoxitus, how it is regulated, and its relationship with degradative autophagy. Researchers will also examine the role of autoxitus in stress signal transmission to neighbouring cells and in the viral life cycle.
Objective
Cells control their content by balancing its synthesis and degradation. Autophagy is a key degradation process capable of engulfing large fractions of cells, including organelles, into double-membrane vesicles called autophagosomes. These fuse with lysosomes causing degradation of their cargo. Secretory pathways, including secretory autophagy, offer an alternative option to remove unwanted materials from cells. However, mechanisms allowing the secretion of larger cellular components are still unknown.
We identified a novel pathway, which we termed autoxitus – for self (auto) exit (xitus) – that leads to the secretion of autophagosomes. This proposal aims at defining the molecular mechanism and regulation of autoxitus. We will first study how specificity and decision-making between secretory autoxitus and degradative autophagy routes is achieved and whether there is cross-regulation. Autophagosomes on the autoxitus route can contain parts of the cytosol, but also large fragments of organelles, raising the question whether the secreted autoxitus vesicles signal to neighbouring cells in a non-cell autonomous manner. We aim to uncover the impact of these signalling processes to determine whether and how autoxitus helps to signal stress conditions or may even deliver material or organelles to other cells. Finally, the role of autoxitus in two (patho-)physiological conditions will be analysed. Since autophagic processes are key to viral particle release, we will study the contribution of autoxitus to the viral life cycle. Furthermore, we will investigate the role of autoxitus in the release of protein aggregates from cells and the resulting seeding propensity.
This proposal will give ground-breaking insight into autoxitus, its molecular underpinnings and physiological consequences. AutoXitus will provide the framework for future integration into numerous cellular pathways.
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.
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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-COG
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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.
60323 FRANKFURT AM MAIN
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.