Project description
Uncovering neuronal secretory pathways
Neurons experience metabolic stress causing damage to proteins and organelles, which then must be cleared to maintain function. While autophagy degrades most of this cellular debris, neurons also secrete some of it into the extracellular space (a secretory pathway), a process that is still poorly understood. Dysregulation of this process is linked to neurodegenerative diseases such as Alzheimer’s. Supported by the Marie Skłodowska-Curie Actions programme, the NEURO-SECRET project aims to use human induced pluripotent stem cell-derived neurons and state-of-the-art molecular tools to visualise neuronal secretory autophagy at high spatiotemporal resolution. By combining bioluminescent/fluorescent reporters with proximity labelling and chemogenetic relocalisation, the project will chart critical regulators and explore ways to modulate this pathway, shedding new light on probing and even treating neurodegeneration.
Objective
Neurons transmit information by connecting with other neurons over long distances through their dendrites and axons. Repeated stimulation places a high metabolic demand on these cells, leading to the accumulation of defective organelles and protein aggregates. To maintain protein homeostasis, neurons rely on constitutive autophagy to remove these damaged proteins and organelles from their dendrites and axons, targeting them for degradation. However, it is becoming increasingly clear that neurons also secrete a part of this autophagic cargo into the extracellular space. The mechanisms governing neuronal secretory autophagy are still poorly understood. The factors that determine whether autophagic cargo is degraded or secreted, as well as the precise neuronal location from which secretory autophagy occurs, remain unknown. Understanding these mechanisms is highly relevant in neurodegenerative diseases, such as Alzheimer’s disease, where the balance between degradative and secretory autophagy is disrupted. In this interdisciplinary project, I will use human iPSC-derived neurons and develop novel molecular tools to elucidate the mechanisms underlying neuronal secretory autophagy. I will employ state-of-the-art bioluminescent and fluorescent reporters to characterize this process with high spatiotemporal resolution, leveraging my experience in studying exosome release during my PhD. Furthermore, I will apply the host lab’s expertise in proximity labeling and chemogenetic relocalization to identify key regulators of neuronal secretory autophagy and explore the potential of modulating secretory autophagy in a cell model for Alzheimer’s disease. Ultimately, this project aims to provide fundamental insights into the mechanisms driving neuronal secretory autophagy and the potential for modulating this process in neurodegenerative diseases.
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 neurobiology
- medical and health sciences basic medicine neurology neurodegenerative diseases dementia alzheimer
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine physiology homeostasis
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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)
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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-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.
3584 CS Utrecht
Netherlands
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