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Title [sv]
Modellering av genomets 3D struktur
Title [en]
Modelling the 3D genome
Abstract [en]
From experiments that count physical contacts between DNA fragments in cells, we learned that chromosomes assemble into a hierarchy of 3D compartments that promote some contacts while excluding others. These compartments help cells coordinate and regulate genetic processes such as DNA replication, repair and gene regulation. However, even though researchers the proteins and genes that enrich close to compartment borders, they have limited understanding of the mechanisms behind compartment formation. We propose research  to close this gap. We will use  algorithms that cluster protein binding data and partition chromosomes into biologically relevant regions. From these regions, we will represent chromosomes as polymer fibres and use simulations to produce 3D structures that we will compare with DNA contact data. Once we determined our model parameters, we will predict changes to the chromosome´s 3D structure in experiments with genetically engineered  fruit fly genomes made by our collaborators. We will also explore how the condensed state of chromosomes in the beginning of the cell´s life affect the unfolded 3D structure, and how 3D compartments change when  chromosomes are located in the centre of the nucleus compared to at to the periphery. As an integrated package, this proposal will combine biophysics models and state-of-the art genetic experiments to address one of the big remaning open problems in cell biology: What governs the spatial organisation of genomes?
Principal InvestigatorLizana, Ludvig
Coordinating organisation
Umeå University
Funder
Period
2018-01-01 - 2021-12-31
National Category
Condensed Matter PhysicsBiophysics
Identifiers
DiVA, id: project:1647Project, id: 2017-03848_VR

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