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Regulation of cell size and cell division in fission yeast

Reference	BBS/E/J/000CA611
Principal Investigator / Supervisor	Professor Martin Howard
Co-Investigators / Co-Supervisors
Institution	John Innes Centre
Department	John Innes Centre Department
Funding type	Research
Value (£)	39,590
Status	Completed
Type	Institute Project
Start date	01/01/2016
End date	31/03/2017
Duration	14 months

Abstract

The mechanistic basis of cell size control is not properly understood in any cell type. In dividing cells, cell size homeostasis can be achieved through thresholding, with cells growing to a minimal size before division. Fission yeast is a well-studied model for size control, offering many experimental advantages, including regular shapes and division patterns. Pathways of conserved protein kinases that affect cell size have been identified, but it is not generally agreed how a minimal size is sensed. Here, we will dissect cell size control in fission yeast through predictive mathematical modelling and experiments. The intrinsically quantitative nature of cell size control makes this approach highly appropriate. We recently proposed an initial cell size control model involving Cdr2, a dose-dependent mitotic activator that regulates Cdk1/Cyclin B through Wee1 inhibition. Cdr2 localizes to a band of cortical nodes around the nucleus, with its nodal concentration scaling with cell surface area. Cdr2-encoded size information can then be transmitted across the cell to regulate the downstream cell cycle machinery. Here, we will investigate further these size scaling properties, by studying two key properties of Cdr2: its clustering to form nodes, and nodal localization to a region overlying the nucleus. We will construct mathematical models of clustering based on aggregation-fragmentation, also incorporating nuclear shuttling and inhibition by another protein Pom1. We will test model predictions by live-cell confocal, single particle TIRF and superresolution microscopy. Finally, we will study how cell size information in the nodes is transmitted to the Spindle Pole Body where mitotic decision-making occurs. We hypothesize this takes place via concentration gradients or through signal corralling by diffusion barriers. We will test these ideas by microscopy and identification of possible barriers, such as Endoplasmic Reticulum membranes.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Microbiology, Systems Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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