Innovating Works

CHROMOREP

Financiado
Reconstitution of Chromosome Replication and Epigenetic Inheritance
A PubMed search for ‘epigenetic’ identifies nearly 35,000 entries, yet the molecular mechanisms by which chromatin modification and gene expression patterns are actually inherited during chromosome replication — mechanisms which l... A PubMed search for ‘epigenetic’ identifies nearly 35,000 entries, yet the molecular mechanisms by which chromatin modification and gene expression patterns are actually inherited during chromosome replication — mechanisms which lie at the heart of epigenetic inheritance of gene expression — are still largely uncharacterised. Understanding these mechanisms would be greatly aided if we could reconstitute the replication of chromosomes with purified proteins. The past few years have seen great progress in understanding eukaryotic DNA replication through the use of cell-free replication systems and reconstitution of individual steps in replication with purified proteins and naked DNA. We will use these in vitro replication systems together with both established and novel chromatin assembly systems to understand: a) how chromatin influences replication origin choice and timing, b) how nucleosomes on parental chromosomes are disrupted during replication and are distributed to daughter chromatids, and c) how chromatin states and gene expression patterns are re-established after passage of the replication fork. We will begin with simple, defined templates to learn basic principles, and we will use this knowledge to reconstitute genome-wide replication patterns. The experimental plan will exploit our well-characterised yeast systems, and where feasible explore these questions with human proteins. Our work will help explain how epigenetic inheritance works at a molecular level, and will complement work in vivo by many others. It will also underpin our long-term research goals aimed at making functional chromosomes from purified, defined components to understand how DNA replication interacts with gene expression, DNA repair and chromosome segregation. ver más
30/04/2022
2M€
Duración del proyecto: 81 meses Fecha Inicio: 2015-07-28
Fecha Fin: 2022-04-30

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2022-04-30
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-ADG-2014: ERC Advanced Grant
Cerrada hace 10 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
THE FRANCIS CRICK INSTITUTE LIMITED No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5