LoopingDNA
Financiado
Bottom up biophysics approach to resolve the looping structure of chromosomes
How is DNA spatially organized in our cells? What are the mechanisms that shape chromosomes and how does their 3D architecture direct their function? Recent years have shown that the spatial structure of the genome is of pivotal i...
How is DNA spatially organized in our cells? What are the mechanisms that shape chromosomes and how does their 3D architecture direct their function? Recent years have shown that the spatial structure of the genome is of pivotal importance for its biological function. Yet, the basic physics of the formation and regulation of its 3D structure has remained unclear. This proposal aims to understand the fundamental structure of chromosomes using a bottom up biophysics approach, from looping at the single-molecule level to higher levels of complexity. We focus on so-called SMC protein complexes (SMC = Structural Maintenance of Chromosomes). These ring-shaped proteins are a unique new type of molecular motors that can extrude large loops of DNA that are thought to be the basis of chromosome structure. Our group’s recent breakthrough discovery of the looping motor function of condensin SMC paved the way to now answer major open questions, such as the motor mechanism of SMCs; how SMCs handle realistic chromosomal fibers loaded with DNA-binding proteins; how looping relates to gene expression; and whether it is evolutionary conserved from bacteria to man. By answering these questions using single-molecule assays, we will resolve the basic mechanics of the SMC-induced looping of DNA. We will extend this to even build a chromosome from the bottom up, in a ‘genome-in-a-box’ approach where we will take genome-length bare DNA and add SMC protein complexes and other DNA-processing proteins. Such a well-controlled bottom-up approach – which to our knowledge is unique – can be expected to generate a radically new understanding of the physical forces and protein systems that shape chromosomes. We are confident that our powerful single-molecule biophysics tools, in collaboration with working with the world’s best biochemists, will enable to disentangle the fundamental looping architecture of chromosomes that is so essential to all of life.
ver más
Duración del proyecto: 61 meses
Fecha Inicio: 2020-05-12
Fecha Fin: 2025-06-30
Fecha Fin: 2025-06-30
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2020-05-12
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2019-ADG:
ERC Advanced Grant
Cerrada
hace 5 años
Presupuesto
El presupuesto total del proyecto asciende a
3M€
Líder del proyecto
TECHNISCHE UNIVERSITEIT DELFT
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
350.00K€ |
Participante