Project description
Membrane quality control and IRGQ in neurodegeneration
Inflammation in the brain is linked to the onset and progression of neurodegenerative diseases, yet effective mechanism-based treatments remain lacking. One important cause may be defects in autophagy, the cell’s recycling and quality-control system, which clears or repurposes damaged components to maintain cell health. Recent work identified a new protein named IRGQ, which decides whether damaged material is routed for lysosomal degradation or released from the cell, a process that may influence inflammation. With the support of the Marie Skłodowska-Curie Actions programme, the MIND project will study how IRGQ protects cells and controls inflammatory signals. The project will examine how IRGQ loss affects brain health across the lifespan, laying the groundwork for future therapeutic strategies.
Objective
Neurodegenerative diseases and chronic brain inflammation affect millions and still lack effective, mechanism-based treatments. Failures in cellular quality control such as autophagy fuel neuro-inflammation and neuro-degeneration. Our recent work (Herhaus, Cell 2024) identified IRGQ as a new autophagy receptor which directs cargo either to lysosomal degradation (degradative autophagy) or to membrane presentation and cell release (secretory autophagy). IRGQ is essential in maintaining membrane integrity and limiting inflammatory signalling. Our new preliminary data show that IRGQ loss alters immune-synapse readouts and reveal IRGQ as a scaffold for the autophagy initiation machinery and vesicle trafficking regulators—clear motivation to probe brain inflammation and early neurodegeneration in vivo.
Our proposal, MIND (Membrane quality control and IRGQ in Neurodegeneration) combines strong molecular biology with in vivo disease relevance. Building on recent structural and functional evidence that IRGQ binds core autophagy proteins and controls immune cargo, we will: (1) define, with precision, how IRGQ engages the autophagy machinery to route cargo; (2) map how stress reshapes this routing and defines inflammatory signalling; and (3) test consequences in the brain across the lifespan.
We bring unique resources. A novel, unpublished, viable full-body IRGQ knockout mouse, with aged cohorts already available; and advanced molecular expertise in autophagy combined with cutting-edge imaging and proteomics platforms to conduct cell-based screens, and multi-omics and histopathology of our mouse model.
Within 24 months, we aim to characterise IRGQ as a molecular switch that coordinates degradative and secretory autophagy to safeguard cellular integrity and restrains neuroinflammation. The expected outcomes include mechanistic insights into vesicle fate decisions, disease-relevant in vivo data, and the establishment of IRGQ as a new target for modulating neuroinflammation.
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.
This project's classification has been human-validated.
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.
This project's classification has been human-validated.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences cell biology cell signaling
- medical and health sciences health sciences inflammatory diseases
- medical and health sciences basic medicine neurology
- natural sciences biological sciences molecular biology molecular neuroscience
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)
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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.
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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2025-PF
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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
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