Candida albicans, a major cause of systemic and mucosal fungal infections, is a multimorphic yeast able to survive in different environmental niches. Morphologic switching between yeast form (YF) growth and filamentous form (FF) growth is required for efficient virulence. The involvement of the fork head transcriptional regulator CaFkh2p in the morphologic transition between YF and FF growth in C. albicans will be the focus of this proposal.
Specific Aim #1 will assess if CaFKH2 is regulated at the transcriptional and/or translational level under environmental conditions known to activate the morphologic switch.
Specific Aim #2 will identify genes under CaFkh2p control by monitoring the expression of C. albicans genes involved in morphogenesis, with an emphasis placed on cell cycle regulatory genes, in CaFkh2p-deficient strains.
Specific Aim #3 will determine the relationship between CaFkh2p and known pathways that regulate morphogenesis.
Specific Aim #4 will address the role of B-type cyclins in the CaFkh2p morphogenesis pathway. These studies will define the role of CaFkh2p in C. albicans morphologic switching and will clarify the coordination of morphogenesis and the cell cycle. Ultimately, this work will identify novel drug targets for new therapeutic strategies to combat C. albicans infections.
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