Project description
Insight into somatic mutations of healthy tissue, ageing and disease
Somatic mutations in cells continually increase in healthy tissue, often maintaining homeostasis, modifying cancer genes, and fostering cell plasticity, self-renewal and growth. Though such features decline with age, mutant cells rarely become pathogenic. The ERC-funded MUTAHOME project hypothesises that somatic mutations boost tissue integrity by increasing the fitness of stem/progenitor cells (SPCs) to compensate for age-induced decline. To test this, it will investigate the impact somatic mutations have on SPC fitness in tissues and blood using complementary approaches of evolutionary genetics and stem cell biology. Through the analysis of human tissue and the use of complex mouse models, the project will determine whether the increase in mutant SPCs over time leads to a decline in SPC diversity, eventually increasing disease risk.
Objective
Healthy tissues become progressively populated of clonally expanded cells that have acquired somatic mutations. Often these mutations modify cancer genes promoting cell plasticity, self-renewal, and growth, all features known to decline with ageing. Despite being pervasive across tissues and persistent throughout life, only rarely mutant cells become pathogenic.
Here we hypothesise that somatic mutations enhance tissue integrity by increasing the fitness of stem/progenitor cells (SPCs) to counterbalance their age-induced decline. Increased SPC fitness at the cellular level increases the fitness at the tissue level, thus preserving the overall tissue regenerative potential.
To test this hypothesis, we propose to investigate the effect of somatic mutations on SPC fitness in solid tissues and blood using complementary and synergistic approaches specific to our teams, bridging the historically distinct fields of evolutionary genetics and stem cell biology.
Through the analysis of human tissues and the use of complex mouse models, we will dissect the interactions between mutant SPCs and their niche, at homeostasis and upon insults. We will determine whether the expansion of mutant SPCs over time leads to a progressive decline in SPC diversity, which eventually increases disease risk.
We will adopt a progressive approach. We will first characterise the mutant clone (WP1) and its crosstalk with the niche (WP2) at homeostasis. We will then test the response of mutant clone and niche to physiological (WP3) and pathological (WP4) challenges. We will finally assess the occurrence of a multiorgan crosstalk conveyed by mutant blood on mutant solid tissues (WP5).
This study will radically transform our understanding of tissue homeostasis and clarify the relationship between somatic mutations, ageing and disease. A deeper knowledge of the mechanisms that maintain the homeostatic equilibrium over time is the first step to guide intervention and disease prevention.
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 genetics mutation
- medical and health sciences clinical medicine oncology
- 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.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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-ERC-SYG - HORIZON ERC Synergy 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-2024-SyG
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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.
NW1 1AT London
United Kingdom
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