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Understanding mammalian interphase genome structure in mouse ES cells (360G-Wellcome-206291_Z_17_Z)

The folding of genomic DNA from the beads-on-a-string like structure of nucleosomes into higher order assemblies is critically linked to nuclear processes, but it is unclear to what degree it is a cause or consequence of function. We aim to understand whether the Nucleosome Remodeling and Deacetylation (NuRD) complex regulates chromatin structure to control transcription, or whether it is NuRD’s regulation of transcription that results in global changes in chromosome structure. We have calculated the first 3D structures of entire mammalian genomes using a new chromosome conformation capture procedure, which combines imaging with Hi-C processing of the same single cell. Our objectives are now: To study: 1) how interphase mammalian genome structure is established in G1; 2) the factors that drive this formation and; 3) how this organisation is regulated by chromatin remodellers (such as the NuRD complex) as mESC’s differentiate. To build a dedicated bespoke microscope for 3D double helix point spread function detection with light sheet activation, optimised for 3D single-molecule/super-resolution imaging of proteins such as the NuRD complex. To combine 3D super-resolution imaging and the biochemical processing steps of single cell Hi-C to directly correlate binding of protein complexes to regions of the structures.

£2,031,409

05 Apr 2017

Grant details
Amount Awarded 2031409
Applicant Surname Laue
Approval Committee Science Interview Panel
Award Date 2017-04-05T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title Collaborative Award in Science
Internal ID 206291/Z/17/Z
Lead Applicant Prof Ernest Laue
Other Applicant(s) Dr Brian Hendrich, Prof David Klenerman
Planned Dates: End Date 2022-05-01T00:00:00+00:00
Planned Dates: Start Date 2017-05-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
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