Coordination of chromosome unlinking and segregation (360G-Wellcome-200782_Z_16_Z)

£1,625,956

The objective is to understand mechanistically how the bacterial chromosome is organized and processed throughout the cell cycle, by addressing the molecular mechanism by which the SMC complex, MukBEF, acts in chromosome organisation and segregation. This will also generally inform mechanisms of SMC action, a crucial process in normal and pathological chromosome management in all organisms. The proposed research will use state-of-the-art methods to minimise ensemble averaging. By using quantitative live-cell single-molecule imaging that allows visualization of the assembly and action of molecular machines, alongside methods that allow the rapid production and removal of specific proteins, and which interfere with normal protein interactions, it will enable mechanistic in vivo biochemistry that will be complemented by elegant genetics and in vitro biochemistry. We will progress our work showing that the interaction between MukBEF and, TopoIV, is essential for timely chromosome unlinking, and that MatP, which binds multiple sites within the replication termination region, regulates the spatial cellular distribution of MukBEF and TopoIV. Finally, we will characterize the mechanism by which localised MukBEF clusters act to position and segregate newly replicated oris, while leading to global chromosome organization, timely chromosome segregation and efficient repair.

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Grant Details

Amount Awarded 1625956
Applicant Surname Sherratt
Approval Committee Science Interview Panel
Award Date 2016-04-05T00:00:00+00:00
Financial Year 2015/16
Grant Programme: Title Investigator Award in Science
Internal ID 200782/Z/16/Z
Lead Applicant Prof David Sherratt
Partnership Value 1625956
Planned Dates: End Date 2021-03-01T00:00:00+00:00
Planned Dates: Start Date 2016-09-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East