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TRANSIT-ND

Financiado

Tandem Repeats Associated with Neurogenomic Somatic Instability and Neurodegener...

"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 strategi... ver más

31/05/2027

BUNDESMINISTERIUM...

1M€

Presupuesto del proyecto: 1M€

Líder del proyecto

BUNDESMINISTERIUM FUER GESUNDHEIT No se ha especificado una descripción o un objeto social para esta compañía.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-03-23

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

ERC-2021-STG: ERC STARTING GRANTS

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BUNDESMINISTERIUM FUER GESUN...

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Últimas noticias

29-11-2024: IDAE En las últimas 48 horas el Organismo IDAE ha otorgado 4 concesiones

29-11-2024: ECE En las últimas 48 horas el Organismo ECE ha otorgado 2 concesiones

29-11-2024: CMVAMADRID En las últimas 48 horas el Organismo CMVAMADRID ha otorgado 37 concesiones

Duración del proyecto: 62 meses Fecha Inicio: 2022-03-23
Fecha Fin: 2027-05-31

Presupuesto del proyecto 1M€

Descripción del proyecto "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."

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