TopoGenomics
Financiado
Topological interactions as functional regulators of the eukaryotic genome movi...
Topological interactions as functional regulators of the eukaryotic genome moving beyond intramolecular looping
Topological interactions between distant DNA segments play fundamental roles in the function of eukaryotic genomes. While tremendous progress has been made in understanding the molecular mechanisms shaping intramolecular chromosom...
Topological interactions between distant DNA segments play fundamental roles in the function of eukaryotic genomes. While tremendous progress has been made in understanding the molecular mechanisms shaping intramolecular chromosome loop structures, limitations in our ability to distinguish specific chromosome conformations between paired molecules has hindered research into the role of interactions across separate chromosomal DNA molecules. Our recent development of an approach allowing analysis of contacts between sister chromatids now provides an opportunity for research into topological interactions to enter a new phase. Initial analyses with sister chromatid-sensitive Hi-C (scsHi-C) have indicated enormous potential to elucidate the mechanisms by which sister-chromatid conformation controls processes as varied as DNA repair, gene regulation and the segregation of mitotic chromosomes. To fulfil this potential, we will now develop next-generation scsHi-C technology to generate high-resolution genome-wide conformation maps of sister chromatids, along with the establishment of a machine learning-based computational framework to systematically detect topological structures in sister chromatids. This will be complemented with an imaging-based super-resolution approach to trace sister-chromatid fibers in thousands of individual cells. These core advances will allow us to map distinct sister-chromatid contact domains and identify associated molecular signatures, understand how loop-extruding and cohesive cohesin interact to shape replicated chromosomes, and determine how epigenetic modifications control pairing between sister chromatids. Together, these developments will allow us to make key advances in understanding a fundamental yet largely neglected aspect of chromosome biology—how replicated sister chromatids topologically interact to support maintenance, expression, and segregation of eukaryotic genomes.
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Duración del proyecto: 60 meses
Fecha Inicio: 2021-08-13
Fecha Fin: 2026-08-31
Fecha Fin: 2026-08-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2021-08-13
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2020-ADG:
ERC ADVANCED GRANT
Cerrada
hace 4 años
Presupuesto
El presupuesto total del proyecto asciende a
3M€
Líder del proyecto
INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
304.60K€ |
Participante