Project description
Mapping DNA instability in dementia
Dementia and related neurodegenerative diseases are among the leading causes of disability worldwide. Despite their impact, the biological triggers of neuronal degeneration are poorly understood. Clues have emerged from rare genetic disorders caused by expansions of repetitive DNA sequences, known as tandem repeats, which can destabilise neurons. But their role in common, age-related diseases remains unclear. The EU-funded TRANSIT-ND project aims to investigate whether variations and instability in these DNA repeats contribute to widespread neurodegeneration. Using liquid biopsies, ultra-deep long-read sequencing and advanced brain imaging, researchers will map where instability occurs and how it affects neural circuits. By combining multi-omics analyses with laboratory validation, TRANSIT-ND aims to uncover shared mechanisms, and potential therapeutic targets, across major neurodegenerative disorders.
Objective
"Dementia and other neurodegenerative diseases are among the leading causes of disability worldwide and have an immense societal impact due to lack of effective treatments. For developing better preventive and therapeutic strategies, it is essential to clarify their still largely elusive genetic basis and pathophysiology. Emerging insights from the study of rare hereditary repeat expansion disorders caused by elongations of repetitive DNA sequences (""tandem repeats"" (TRs)) indicate that TRs could induce instability of neuronal DNA (""neurogenomic somatic instability""), and thereby instigate molecular changes that lead to neuronal degeneration. However, the role of highly prevalent TR variations or their somatic instability in the pathogenesis of common age-associated neurodegenerative diseases is unknown. Here, I aim to assess the role of TRs and their somatic instability in the pathogenesis of neuronal degeneration, the defining hallmark of all neurodegenerative diseases. To this end, I will 1) systematically identify TRs whose size or somatic instability are related to neuronal degeneration in the general population and/or disease severity in repeat expansion disorders, using an innovative approach combining ""liquid biopsy"" of neuronal tissue, high-throughput ultra-deep long-read DNA sequencing and ultrasensitive biomarkers of neuronal degeneration, 2) delineate the neuroanatomical pathways affected by TR somatic instability through comprehensive neuroimaging analyses, and 3) disentangle the underlying molecular and cellular mechanisms, using an extensive integrative multi-omics approach with experimental validation in neuronal cell lines and post-mortem human brain tissue. The wealth of unique insights from TRANSIT-ND could substantially increase our understanding of the pathogenesis of neuronal degeneration and provide shared targets for the prevention and treatment of a range of different neurodegenerative diseases that afflict millions of people globally."
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
- natural sciences biological sciences genetics DNA
- medical and health sciences basic medicine physiology pathophysiology
- medical and health sciences basic medicine neurology neurodegenerative diseases dementia
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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)
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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
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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-2021-STG
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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.
53127 Bonn
Germany
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