Objective
Multiple deletions in mtDNA give rise to a variety of neuromuscular symptoms, often associated with genetic inherited disorders and aging and they have been reported in patients with neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases. In spite of its medical importance, not much is yet known about the mechanisms by which mtDNA deletions are formed. Progressive external ophtalmoplegia (PEO) is one of the conditions characterized by the accumulation of mtDNA deletions. This disease is caused by mutations in components of the mtDNA replication machinery, like the DNA polymerase γ (POLγ) and the replicative helicase TWINKLE. Recently, also the helicase-nuclease DNA2 has been found mutated in patients affected by this disorder. The precise function of human DNA2 (hDNA2) has remained elusive. hDNA2 localizes to mitochondria and has the biochemical properties to process four-stranded DNA structure (G-quadruplexes). Interestingly, G-quadruplex DNA associates with mtDNA deletions formation in human diseases.
To dissect the mitochondrial role of hDNA2, I will focus on the mechanism of hDNA2 recruitment to mtDNA. Then I will address the role of DNA2 in mitochondria metabolism and in G-quadruplexes mtDNA metabolism and I will characterize the consequences of disease-associated mutations in DNA2 gene. I will employ a range of in vitro (based on recombinant protein) and in vivo (inducible cell systems and yeast model).
The clarification of the hDNA2 mitochondrial biological function will help to elucidate the mechanism by which mtDNA deletions are formed in mitochondrial disorders. Moreover, MITOQUAD project will lead to a deeper understanding of how mtDNA integrity is maintained, a relevant question for understanding the early development and progress of a large number of mitochondrial disorders, in order to treat or prevent their occurrence.
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 neurology dementia alzheimer
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine neurology parkinson
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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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF-EF-ST - Standard EF
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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) H2020-MSCA-IF-2016
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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.
901 87 UMEA
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.