Morphology-specific hybridization probes were used to screen a cDNA library from Candida albicans in the process of forming hyphae, in order to identify genes that are differentially expressed during morphogenesis. At least 21 different genes, differentially expressed during the dimorphic transition, were identified and cloned. Using transformation techniques we will focus our continuing studies on the mechanisms for controlling gene expression during the dimorphic response.
The specific aims are to study the role of these genes in dimorphism by genetic manipulation of their expression, constructing null alleles and inappropriately expressed alleles, and to study the regulation of their expression by in vivo and in vitro promoter analysis. Studies on yeast-hyphal dimorphism in Candida albicans are made compelling by the wide range of pathogenic fungi that exhibit the phenomenon and the possible role that hyphal forms play in the pathogenesis of Candida albicans. Our experiments on the control of transcription of differentially expressed genes are aimed at understanding dimorphism, rather than transcription per se, and employ a range of molecular genetic techniques now available. Knowledge of the mechanisms responsible for the differential expression of gene will be a significant step in our understanding of how Candida albicans responds to its environment and regulates the dimorphic response.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM047727-04
Application #
2185156
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1992-05-01
Project End
1996-04-30
Budget Start
1994-10-01
Budget End
1996-04-30
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Georgetown University
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
McNemar, Mark D; Fonzi, William A (2002) Conserved serine/threonine kinase encoded by CBK1 regulates expression of several hypha-associated transcripts and genes encoding cell wall proteins in Candida albicans. J Bacteriol 184:2058-61
Fonzi, W A (2002) Role of pH response in Candida albicans virulence. Mycoses 45 Suppl 1:16-21
Porta, A; Wang, Z; Ramon, A et al. (2001) Spontaneous second-site suppressors of the filamentation defect of prr1Delta mutants define a critical domain of Rim101p in Candida albicans. Mol Genet Genomics 266:624-31
El Barkani, A; Kurzai, O; Fonzi, W A et al. (2000) Dominant active alleles of RIM101 (PRR2) bypass the pH restriction on filamentation of Candida albicans. Mol Cell Biol 20:4635-47
Yesland, K; Fonzi, W A (2000) Allele-specific gene targeting in Candida albicans results from heterology between alleles. Microbiology 146 ( Pt 9):2097-104
Porta, A; Ramon, A M; Fonzi, W A (1999) PRR1, a homolog of Aspergillus nidulans palF, controls pH-dependent gene expression and filamentation in Candida albicans. J Bacteriol 181:7516-23
Sharkey, L L; McNemar, M D; Saporito-Irwin, S M et al. (1999) HWP1 functions in the morphological development of Candida albicans downstream of EFG1, TUP1, and RBF1. J Bacteriol 181:5273-9
Ramon, A M; Porta, A; Fonzi, W A (1999) Effect of environmental pH on morphological development of Candida albicans is mediated via the PacC-related transcription factor encoded by PRR2. J Bacteriol 181:7524-30
Fonzi, W A (1999) PHR1 and PHR2 of Candida albicans encode putative glycosidases required for proper cross-linking of beta-1,3- and beta-1,6-glucans. J Bacteriol 181:7070-9
De Bernardis, F; Muhlschlegel, F A; Cassone, A et al. (1998) The pH of the host niche controls gene expression in and virulence of Candida albicans. Infect Immun 66:3317-25

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