Research Projects

The yeast Candida albicans is the most abundant fungus on human mucosal surfaces. C. albicans is placed in the critical priority group of human fungal pathogens by World Health organization (WHO) is published for the first time in 2022. C. albicans can form biofilms, that represent a major fungal virulence factor which makes the fungus more tolerant to antifungals, the host immune system, and other environmental perturbations than free-floating planktonic cells. The biofilm-forming gene network is controlled both by transcription regulators and chromatin modifiers including histone H3 variant. The occurrence of the biofilm gene network in the CTG clade is considered as a relatively recent acquisition and among the Candida clade spp. (CTG clade spp.), only a few species closely related to C. albicans can form efficient biofilms. Strikingly, functions of several well-characterized genes of Saccharomyces cerevisiae have been rewired in C. albicans for example, Ndt80, a transcription factor controlling sporulation in S. cerevisiae, has changed its function from regulating sporulation to biofilm formation in C. albicans. Interestingly, a CTG clade-specific histone H3 variant (H3VCTG) plays a role in biofilm formation in diploid yeast species of the CTG clade including C. albicans. However, its role is unknown in haploid yeast species of the CTG clade that can sporulate but unable to form biofilms. The amino acid sequence analysis of histone H3 variant between biofilm-forming species (Candida albicans, Candida dubliniensis, and Candida tropicalis) and biofilm non-forming species (C. lusitaniea, Debaryomyces hansenii, and Meyerozym guilliermondii) revealed the amino acid sequence differences at residue namely, 102 and 124. Amino acid residue glycine at position 102 is changed to serine (G-S) whereas methionine at position 124 is changed to isoleucine (M-I) in non-biofilm forming haploid yeast species of the CTG clade as compared to C. albicans. However, the role of histone H3 variant in non-biofilm-forming species of the CTG clade is unknown. Thus, in this proposal, we aim to investigate the role of histone H3 variant in non-biofilm forming species such as C. lusitaniea, D. hansenii, and M. guilliermondii that can undergo sporulation Using knockout approaches null mutants of histone H3 variant will be generated and their sporulation efficiency will be determined. By site-direct mutagenesis amino acid position at 102 and 124 will be changed similar to C. albicans in these non-biofilms forming haploid yeasts and biofilm formation will be examined. Further, transcript profiling and genome-wide binding studies will be conducted to reveal the mechanisms of variant histone H3 change in function from sporulation to biofilm formation. Altogether, this project proposal will reveal insights into acquiring of a new function of H3VCTG from sporulation in haploid yeast to the biofilm formation in diploid yeast species of the fungal-specific CTG clade.