Award details

Genetic regulation of phenotypic heterogeneity and its benefits for cell populations in fluctuating environments

Reference	BB/C506656/1
Principal Investigator / Supervisor	Professor Simon Avery
Co-Investigators / Co-Supervisors
Institution	University of Nottingham
Department	Sch of Biology
Funding type	Research
Value (£)	192,481
Status	Completed
Type	Research Grant
Start date	01/03/2005
End date	29/02/2008
Duration	36 months

Abstract

This proposal tackles the topical question of phenotypic (non-genotypic) heterogeneity that occurs naturally in all cell populations. It has been proposed (but not tested) in recent papers that such cell-to-cell heterogeneity within isogenic populations has evolved as an important insurance mechanism for microorganisms; creating cell subpopulations that are pre-equipped for varied activities as needs may arise (e.g. when faced with adverse conditions), but without the permanent metabolic costs of constitutive expression. In support of this hypothesis, we have shown that such phenotypic heterogeneity in the yeast Saccharomyces cerevisiae is not purely stochastic (random), but is driven by ordered cellular processes that are subject to genetic control. Furthermore, we have specifically identified Sod1p and Gsh1p/Ycf1p as heterogeneity generators of cellular copper and cadmium resistance, respectively. This project aims to build on this recent work to elucidate for the first time a rational genetic basis for heterogeneity among single cells within clonal cultures. First, we propose to complete our characterisation of the regulatory mechanisms underlying heterogeneous Sod1p and Gsh1p/Ycf1p- dependent resistance to metals and other stressors. This information will subsequently allow us to test the central hypothesis: that ordered genetic regulation driving phenotypic heterogeneity provides a competitive advantage in cell populations that may face environmental change. The findings could have important repercussions for our understanding of microbial fitness and persistence in industrial and other settings.

Summary

unavailable

Committee	Closed Committee - Plant & Microbial Sciences (PMS)
Research Topics	X – not assigned to a current Research Topic
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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