BrainBreaks
Financiado
DNA Breaks Shape Neural Genome Heterogeneity
Neural progenitor cells undergo tens of thousands of cell divisions to generate the 80 billion neurons in a human brain. In neural progenitor cells, replication stress can lead to recurrent DNA break clusters (RDCs). Joining of tw...
Neural progenitor cells undergo tens of thousands of cell divisions to generate the 80 billion neurons in a human brain. In neural progenitor cells, replication stress can lead to recurrent DNA break clusters (RDCs). Joining of two RDC breaks may introduce somatic genomic diversity. On the other hand, unbalanced genomic mosaicism in neural progenitor cells may lead to brain cancer and neuropsychiatric disorders. This proposal will test whether cell-autonomous DNA lesions that accumulate during rapid progenitor division contribute to the genetic heterogeneity found across neuronal cell populations.
Aim 1 will elucidate how replication stress drives recurrent break clusters in the neural progenitor cell genome. We will evaluate whether chromatin loop extrusion mechanistically contributes to breakage repairs, and thus helps shape genomic structure variations.
Aim 2 will quantify the extent and impact of tissue-specific recurrent break clusters in the embryonic brain. I will create a mouse model to identify DNA breaks in temporal and cell-type-specific manner across the entire population of neuronal progenitor cells.
Aim 3 will evaluate whether replicative stress drives the recurrent genomic alteration in the RDC-containing gene during embryonic neurogenesis. We will investigate one of the RDC-containing gene Neurexin 1, where deletion or truncation results in neurological disorders.
By combining a powerful in vitro cell line-based tool, versatile in vivo mouse models, and cutting-edge multi-omics approaches, we will uncover the mechanisms that are critical to the fields of genomics and developmental neuroscience and may also provide valuable new insights into neuropsychiatric disorders and tumor biology.
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Duración del proyecto: 62 meses
Fecha Inicio: 2020-10-28
Fecha Fin: 2025-12-31
Fecha Fin: 2025-12-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2020-10-28
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2020-STG:
ERC STARTING GRANTS
Cerrada
hace 5 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
871.34K€ |
Participante