Objective
Necrosis contributes critically in devastating human pathologies such as stroke, ischemia, and age-associated neurodegenerative disorders. Ageing increases susceptibility to neurodegeneration, in diverse species ranging from the lowly nematode Caenorhabditis elegans to humans. The mechanisms that govern necrotic neurodegeneration and its modulation by ageing are poorly understood. Autophagy has been implicated in necrosis and neurodegeneration, both with pro-survival and a pro-death roles. Autophagic flux declines with age, while induction of autophagy enhances longevity under conditions such as low insulin/IGF1 signalling and dietary restriction, which extend lifespan across diverse taxa. Our recent findings indicate that organelle-specific autophagy, including mitophagy, pexophagy and nucleophagy, is an important, evolutionarily conserved, determinant of longevity. We propose to dissect the molecular underpinnings of neuron vulnerability to necrosis during ageing, focusing on cargo-specific macroautophagy. To this end, we will implement a multifaceted approach that combines the power and versatility of C. elegans genetics with advanced, in vivo neuronal imaging and microfluidics technology. Our objectives are fourfold. First, we will monitor autophagic flux of organellar cargo, during neurodegeneration, under conditions that alter lifespan and identify mediators of organelle-specific autophagy in neurons. Second, we will conduct genome-wide screens for modifiers of age-inflicted neurodegeneration. Third, we will interrogate nematode models of human neurodegenerative disorders for organelle-specific autophagy and susceptibility to necrosis, upon manipulations that alter lifespan. Fourth, we will investigate the functional conservation of key mechanisms in mammalian models of neuronal necrosis. Together, these studies will deepen our understanding of age-related neurodegeneration and provide critical insights with broad relevance to human health and quality of life.
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 dementia alzheimer
- medical and health sciences basic medicine neurology stroke
- medical and health sciences basic medicine neurology parkinson
- medical and health sciences basic medicine neurology amyotrophic lateral sclerosis
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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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H2020-EU.1.1. - EXCELLENT SCIENCE - 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.
ERC-ADG - Advanced Grant
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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-2015-AdG
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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.
700 13 IRAKLEIO
Greece
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.