Objective
The basic mechanisms of stem cell malfunction during aging are poorly understood even though they underlie the regenerative decline of most organs and tissues as we age. Based on our recent contributions (Nature 2014, Nature 2016), the fields of tissue regeneration and aging converge on the key role of the quiescent state, the preferred state of stem cells in low turnover tissues such as skeletal muscle. Our unifying hypothesis is that stem-cell quiescence maintenance, which requires active proteostasis (protein homeostasis), lies at the basis of stemness, and that its substitution by a senescence state in aging impairs regeneration. How these variables connect to drive stem cell aging is not known. Crucial experimental systems in this proposal are sensitive reporter mice for proteostasis, senescence and quiescence/fate in aging muscle stem cells. The project is divided as follows: Objective 1. Proteostasis and stem cell quiescence maintenance: tracing proteostasis in quiescent stem cells from autophagy and chaperone-mediated autophagy (CMA) reporter mice during aging / impact of autophagy/CMA loss on quiescence and regeneration / molecular regulators of proteostasis. Objective 2. Proteostasis and quiescent stem cell heterogeneity and fate: asymmetric segregation of proteotoxic waste as an instructor of stem cell heterogeneity and regenerative fate. Objective 3. The quiescence-to-senescence-switch in aging muscle stem cells: tracing and isolating senescent stem cells in senescence-cell reporter mice during aging / impact of senescent cell ablation on regenerating aged muscle. Objective 4. Circadian regulation in the quiescent stem-cell state: impact of aging on circadian rhythms and consequences for quiescence maintenance and regeneration. We expect that completion of these objectives will provide new fundamental knowledge on stem-cell biology, regeneration and aging.
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 biochemistry biomolecules proteins
- medical and health sciences medical biotechnology cells technologies stem cells
- 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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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-2016-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.
08002 Barcelona
Spain
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.