Award details

Adapting to zinc deficiency and disulphide stress in Streptomyces coelicolor

Reference	BB/C503854/1
Principal Investigator / Supervisor	Dr Mark Paget
Co-Investigators / Co-Supervisors
Institution	University of Sussex
Department	Sch of Life Sciences
Funding type	Research
Value (£)	240,926
Status	Completed
Type	Research Grant
Start date	16/11/2004
End date	15/11/2007
Duration	36 months

Abstract

Zinc is an essential metal in all organisms and plays key roles in enzyme catalysis as well as protein structure, where cysteine is the preferred ligand. The primary response to zinc deficiency in many bacteria is the expression of a high-affinity zinc-specific ABC transporter. We have discovered two novel strategies for coping with zinc deficiency in the antibiotic producing bacterium Streptomyces coelicolor. The first involves the expression of alternative ribosomal proteins that, unlike their standard counterparts, are unlikely to contain zinc. The second involves the induction of the SigR regulon, which includes enzymes (e.g. thioredoxin) that repair cysteine thois that might be more exposed to oxidation when zinc is deficient. We propose to: (1) use a rapid targeted mutagenesis technique to isolate a S. coelicolor zinc uptake mutant that should have a zinc-depleted cytoplasm; (2) use acid-trapping techniques to determine the in vivo redox state of selected zinc-binding proteins during zinc deficiency and oxidative stress; (3) investigate the role of the putative zinc-free ribosomal protein paralogues by deleting each respective gene from the S. coelicolor genome; (4) monitor, by two dimensional gel electrophoresis, changes in ribosomal protein complement during zinc deprivation and/or oxidative stress (5) investigate the susceptibility of the translational machinery to zinc deficiency and oxidative stress, using polysome profiling.

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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