Award details

Coordinate regulation of chitin assembly in Candida albicans

Reference	BB/C510191/1
Principal Investigator / Supervisor	Professor Neil Andrew Robert Gow
Co-Investigators / Co-Supervisors
Institution	University of Aberdeen
Department	School of Medical Sciences
Funding type	Research
Value (£)	242,655
Status	Completed
Type	Research Grant
Start date	14/03/2005
End date	13/06/2008
Duration	39 months

Abstract

Chitin is one of two major structural polysaccharides in fungi. Because it is essential for fungal viability and is not present in mammals, it is a key target for the design of specific antifungal drugs to treat fungal infections which are increasingly common and frequently life-threatening in immunocompromised patients. Chitin synthesis in the major human fungal pathogen Candida albicans is achieved via 4 chitin synthase (CHS) genes. Here we propose an integrated and systematic analysis of the individual and collective roles of these chitin synthases and their regulation. We propose to investigate two major questions that are of importance to chitin synthesis in all fungi: (a) how chitin fibrils of distinct and different architecture are generated and (b) how the activation of the four CHS genes is regulated by signal transduction pathways and transcriptional activation. We have shown already that long and short chitin fibrils are synthesised by all fungi although the underlying enzymology is not understood. We have also demonstrated in pilot studies that at least three signal transduction pathways are involved in CHS gene expression including Slt2 (CaMkc1), Hog1 and a previously unsuspected pathway regulated by Ca2 plus, the calcineurin phosphatase Cna1 and its downstream transcription factor Crz1. Accordingly we will: (i) create and analyse a complete set of single and multiple chs mutants and investigate Chs function, chitin fibril morphogenesis in mutants and microsomal enzyme preparations that isolate individual isoenzymes. (ii) Investigate how signalling pathways under various conditions of cell wall stress regulates the expression of individual CHS genes. (iii) Investigate the promoter sequences that are required to achieve this differential gene regulation. Since chitin is the key polysaccharide that determines the strength and shape of most fungi and because chitin is the second most abundant biopolymer on earth these studies will provide fundamental information about chitin synthesis for understanding fungal growth and differentiation. It will also facilitate the rational exploitation of chitin as a therapeutic drug target.

Summary

unavailable

Committee	Closed Committee - Plant & Microbial Sciences (PMS)
Research Topics	Microbiology, Pharmaceuticals
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

I accept the terms and conditions of use (opens in new window)

export PDF file

back to list new search