Genome-wide identification of regulators of morphogenetic variability in the human pathogenic yeast Candida albicans

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Candida albicans is the most important human pathogenic fungus, but also a highly interesting organism with respect to its biology that exhibits many fascinating morphogenetic programs. These include the transition from yeast to filamentous growth, which is controlled by environmental signals, and the spontaneous phenotypic switching to a so-called opaque cell form, which is a requirement for mating between cells of different mating type. The morphological variability and corresponding changes in the gene expression pattern are also important for pathogenicity of this fungus, because they facilitate adaptation to different host niches. The regulation of the various developmental programs is only partially understood and many of the genes controlling them remain to be identified. The C. albicans genome has recently been sequenced, allowing a systematic functional analysis of all genes. As transcriptional activators and repressors play a central role in the regulation of phenotypic traits, the aim of this project is to analyze all transcription factors identified in the C. albicans genome for a possible function in the regulation of morphogenesis. Using a tetracycline-inducible gene expression system developed in our group, the effects of forced expression of each individual transcription factor in various growth conditions on yeast and hyphal growth, whiteopaque switching, and production of chlamydospores, the biological function of which still remains a mystery, will be investigated. This comprehensive analysis will contribute to a detailed understanding of the biology and pathogenicity of C. albicans.