The yeast Candida albicans is a commensal member of the gastrointestinal and urogenital tracts of most healthy humans. However, its capacity to function as an opportunistic pathogen allows it to cause systematic infections of immunocompromised individuals. Over the past two decades, the C. albicans zinc cluster transcription factor family (ZCFs) has been a fascinating subject of research – with studies identifying their roles in virulence, morphogenesis, biofilm formation, drug resistance and many other cellular processes. An understanding of these ZCFs may reveal new targets for therapeutic strategies. 
My work focused on generating genome-wide transcriptional profiling for a large subset of 35 ZCF gain-of-function mutants (GOF) to elucidate the transcriptional profiles among the ZCFs, and on investigating in depth the function of some specific ZCFs in the fungal pathogen.
Transcriptional profiling revealed the target genes that are activated by the ZCF-GOF mutants and provided insight into the underlying roles of the factors. My study focused on establishing the transcriptional regulatory relationship among the ZCFs and understanding the function of some uncharacterized ZCFs. In chapter 2, I selected a set of 35 mostly uncharacterized ZCF, or little is known about them to explore their function using RNA-based transcriptional profiling in collaboration with professor M. Hallett lab. The network approach often shows a specific ZCF-GOF caused activation of expression of other ZCFs, which highlights the extensive interactions among ZCFs. We suggest that most expression changes can be the result of downstream longer-term adaptive responses that induce the expression of intermediate transcription factors. 
In chapter 3, I characterized a new element involved in hyphal development regulation as a previously unstudied Candida-specific ZCF encoded by CaORF19.1604 that I named Rha1 (Regulator of Hyphal Activity). I identified Rha1 through screening a ZCF-GOF library and noting the Rha1-GOF strain was in a filamentous form under yeast growth conditions. I have characterized Rha1 inactivation mutants and GOF alleles, and I explored the Rha1 regulatory network involving Brg1 and Ume6, which are upregulated hyphal activators that appeared in the Rha1-GOF profile to show that Rha1 affects hyphal gene expression and upregulates Brg1/Ume6 and downregulates Nrg1.
In chapter 4, I investigated the role of ZCF4 in cell wall biogenesis, filamentation, biofilm formation, and drug resistance. I explored the ZCF4 function after noting its upregulation in most of the activated ZCF profiles like Rha1-GOF. Zcf4-GOF showed a severe filamentation defect on serum-based medium but exhibited normal filamentation under other cues. I have shown that ZCF4-influenced filamentation is nutrient dependent. 
In chapter 5, I showed the robust ability of C. albicans to use proline as a carbon and nitrogen source by describing CaPut3 as a proline catabolism regulator. The functional studies demonstrated Put3 has a conserved role in regulating proline catabolism in C. albicans and Saccharomyces cerevisiae, but CaPut3 initiates the degradation of proline even in the presence of a rich nitrogen source such as ammonium sulphate.
Collectively, this study established a framework of functional study TFs and generated robust transcriptional data from an activated set of 35 ZCFs to help understand the biology of C. albicans, an important human pathogen.