Award details

Functional proteomic analysis of the hypervirulent Candida glabrata ace2 mutant

Reference	BBS/B/13764
Principal Investigator / Supervisor	Professor Al Brown
Co-Investigators / Co-Supervisors
Institution	University of Aberdeen
Department	School of Medical Sciences
Funding type	Research
Value (£)	177,864
Status	Completed
Type	Research Grant
Start date	01/05/2004
End date	30/04/2007
Duration	36 months

Abstract

Inactivation of the transcriptional regulator Ace2 in Candida glabrata results in a hypervirulent phenotype. Our current proteomic and in vivo data suggest that this is due to induction of severe sepsis as a result of changes in cell wall and/or secretome composition. We intend to investigate this hypothesis using a powerful combination of proteomic, molecular biological and cellular techniques. Initially we will identify further Ace2-dependent components of the C. glabrata cell wall proteome and secretome. In parallel we will analyse the promoters of Ace2 regulated genes to identify the Ace2 consensus sequence. Doxycycline regulatable alleles of Ace2-dependent genes will be constructed and the effect of their inactivation on cytokine induction and virulence will be investigated. We will also determine if ecotopic expression of these genes can suppress the hypervirulence phenotype of C. glabrata ace2 mutants. Finally we will TAP tag C. glabrata Ace2 in order to identify potential regulatory proteins. These experiments will provide new infomation on how C. glabrata Ace2 effects virulence and in the long term may reveal novel opportunities for the development of improved therapeutic, diagnostic and immunological strategies for the management of severe fungal infections. (Joint with BBS/B/10331).

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	Proteomics and Cell Function (PCF) [2003-2004]
Funding Scheme	X – not Funded via a specific Funding Scheme

Associated awards:

BBS/B/10331 Functional proteomic analysis of the hypervirulent Candida glabrata ace2 mutant

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