Objective
Mutations of mtDNA cause mitochondrial diseases and are heavily implicated in the pathophysiology of age-associated diseases and ageing. Low levels of mtDNA mutations are universally present in somatic tissues of all humans and mtDNA mutations have been reported to contribute to age-associated diseases. Somatic mutations of mtDNA often arise during the massive mtDNA replication in embryogenesis and can accumulate postnatally by clonal expansion. Furthermore, ongoing mtDNA replication during adult life also contributes to the burden of mtDNA mutations in mammalian somatic tissues. Mammalian mtDNA is maternally transmitted without germline recombination and this asexual mode of transmission should theoretically lead to a mutational meltdown over generations, the so-called Muller ratchet. At least two poorly understood mechanisms in the maternal germline counteract the transmission of mutated mtDNA from mother to offspring, i.e. the bottleneck mechanism and purifying selection. The bottleneck mechanism ensures that only a fraction of the pool of mtDNA variation in the mother is transmitted to the offspring. The purifying selection functionally tests mtDNA and decreases transmission of mutations. In this proposal we will use powerful mouse models and completely new experimental strategies to study how mammalian mtDNA mutations are inherited and how somatic mtDNA mutations contribute to age-associated disease and ageing. Maternally inherited pathogenic mtDNA mutations often cause life-threatening incurable diseases with failure of multiple organs in humans. Unfortunately, the principles for inheritance of pathogenic mtDNA mutations are often unclear and the knowledge generated in this proposal will give a better basis for genetic counselling. Furthermore, the mechanisms counteracting a mutational meltdown of the non-recombining, maternally transmitted mtDNA is a central question in biology of great basic scientific interest.
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.
- medical and health sciences basic medicine physiology pathophysiology
- natural sciences biological sciences developmental biology
- natural sciences biological sciences genetics mutation
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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)
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.
HORIZON-ERC - HORIZON ERC 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-2023-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.
171 77 STOCKHOLM
Sweden
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.