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The University of Southampton
Biological Sciences

Research project: New regulators of cell division

Currently Active: 
Yes
Project type: 
Studentship

Cell division is a key process that allows cells to proliferate. In some diseases, such as cancer, signaling pathways, which govern cell division, are misregulated. The aim of this project is to identify new players that control cell division. We will look for them among the proteins that are regulated by Cyclin B, and characterise their molecular function in mitosis.

Protein kinase Cdk1, complexed with its activator Cyclin B, is a master-regulator of mitosis. In a recent screen (Hégarat et al, EMBO J, 2020), we identified 125 specific substrates of Cyclin B/Cdk1. Among them were factors controlling essential mitotic pathways, such as Chromosome Passenger Complex (aka Aurora B complex), Ki67, and kinetochore assembly components. Findings of known Cdk1 targets among the previously unidentified substrates assured us about the validity of our approach. Since most of the Cyclin B dependent phosphorylations by Cdk1 indeed are critically important for mitotic progression, we hypothesised that the novel proteins identified in this screen have essential mitotic functions. We will test this by the siRNA depletion and mitotic phenotype analysis of the panel of Cyclin B/Cdk1 substrates. We will study the effects of the CRISPR-based depletion of eight uncharacterised targets of an unknown function along with a number of other targets. From among those we will choose the most promising and interesting candidates to be studied further. This will lead to the identification of new regulatory mechanisms that control mitosis.

This is a genuine, real collaborative effort, which brings our research units together and allows for the accumulation of exciting, top quality data that will be used for preparing an application for a project grant.

Supervisors:

Dr Marcin Przewloka, University of Southampton
Dr Helfrid Hochegger, University of Sussex

PGR student: Mr Fiyinfoluwa Adenekan

Funding provider: BBSRC
Funding dates: 10/2020 – 09/2024

Related research groups

Molecular and Cellular Biosciences
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