Summary of Research
Broad area of research- Cell and Molecular biology/Molecular genetics: Transcription, chromatin and gene regulation
Specific areas- (1) TAF complexes and Mechanism of Transcription in Saccharomyces cerevisiae, Candida albicans; (2) Gene regulation during Iron Homeostasis in Candida albicans (3) Transcriptional Regulatory Network controlling Melanogenesis and pigment disorders using Mouse Melanoma cell lines
The broad area of our research is to dissect the mechanisms and paradigms of gene regulatory networks in eukaryotes. As the transcriptional apparatus is conserved from yeast to humans, we use the model budding yeast Saccharomyces cerevisiae for structure-function analysis of transcriptional coactivator proteins. A second major area of research in the laboratory is to understand the function of novel or diverged transcriptional regulators and transcriptional coactivators in the genome of pathogenic fungus Candida albicans. A third major area of our research is to examine the gene regulatory networks controlling melanogenesis using mouse melanoma cell model.
We employ a wide variety of techniques including molecular genetics, microarray-based transcriptome analysis, proteomics, protein purification, yeast genetics, recombinant protein expression and computational tools.
Structure-function analysis of the Evolutionarily Conserved TAF Transcriptional Coactivators
A plethora of transcriptional coactivator complexes are multisubunit protein machines. Transcriptional activator proteins recruit these coactivator complexes in an ordered manner to the promoters of target genes for transcriptional activation.
We are studying the structure-function relationship of the coactivator TBP-associated factors (TAFs) that are present in both the SAGA histone acetylase complex and TFIID complex. In a recent study, we showed that the TAF9 C-terminal domain is essential for SAGA and TFIID occupancy to all three classes of promoters viz., SAGA-dominated, TFIID-dominated as well as the dual SAGA and TFIID-dominated promoters. The TAF9 C-terminal domain is essential for transcriptional activation by the acidic activator Gcn4 and other activators in yeast. We are now examining what amino acid residues in TAF9 as well as its interacting partner TAF6 contribute to promoter occupancy and transcriptional activation.
These studies will address the specific roles carried out by TAF coactivators in transcription in yeast and other eukaryotes.
Nutrient Control of Gene Regulation in the human fungal pathogen Candida albicans
Transcriptional regulators, aka transcription factors (TFs) play pivotal roles to modulate gene expression in response to environmental signals and host-pathogen response. Using computational tools, we identified over 200 sequences encoding the DNA-binding class of transcriptional regulators in the Candida albicans genome.
Iron is a micronutrient that is essential for cell growth and physiology. Pathogens such as C. albicans have to mobilize iron from iron-poor host environment. In our functional studies of novel TFs, we serendipitously discovered the Cap2-HAP complex as a critical regulator of iron homeostasis gene regulation and virulence of C. albicans. We are now studying how the multiple TFs coordinate the transcriptional control of iron homeostasis gene regulation.
Transcriptional regulatory networks controlling melanogenesis
Diversity of skin color is primarily governed by the type and quantity of melanin pigment in the epidermal layer of skin. Indeed several skin depigmentary disorders such as Vitiligo are also the result of melanin loss in skin. We are interested in the transcriptional regulatory networks that control melanogenesis- hyper-pigmentation and hypo-pigmentation using B16 mouse melanoma cell lines as a model.