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

白色念珠菌是最重要的人类致病真菌，也是一种非常有趣的生物，就其生物学而言，它表现出许多迷人的形态发生程序。这包括由环境信号控制的从酵母到丝状生长的转变，以及自发的表型转换到所谓的不透明细胞形式，这是不同交配类型的细胞之间交配的要求。形态变异和相应的基因表达模式变化对这种真菌的致病性也很重要，因为它们有助于适应不同的宿主生态位。对各种发育程序的调控只是部分了解，许多控制它们的基因仍有待鉴定。最近对白色念珠菌基因组进行了测序，从而对所有基因进行了系统的功能分析。由于转录激活因子和转录抑制因子在表型性状的调控中发挥着核心作用，本项目的目的是分析在白色念珠菌基因组中鉴定的所有转录因子，以寻找其在形态发生调控中的可能功能。利用我们小组开发的四环素诱导基因表达系统，将研究在不同生长条件下强制表达每种转录因子对酵母和菌丝生长、白色不透明切换和衣孢子产生的影响，其生物学功能仍是一个谜。这一综合分析将有助于详细了解白色念珠菌的生物学和致病性。

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.