Emma Lang, majoring in Biology and Spanish (2018), will be studying “The role of the transcription factor Pdc2 in Ascomycota thiamine biosynthesis regulation” with her faculty mentor, Dennis Wykoff, Professor of Biology and Dennis M. Cook Endowed Gregor Mendel Chair in Genetics. Thiamine (also known as vitamin B1) is essential for energy metabolism and, if cells do not have thiamine they die. Ms. Lang will examine how the Pdc2 transcription factor has evolved to upregulate the genes required for thiamine synthesis.
Saccharomyces cerevisiae, the fungus necessary for winemaking, baking and brewing, can make thiamine, but a similar, closely-related yeast, Candida glabrata, lacks the ability to produce thiamine. Both species regulate thiamine metabolism using the transcription factor Pdc2. However, in S. cerevisiae, Pdc2 also regulates sugar breakdown, and Pdc2 is essential for survival. C. glabrata is an emerging fungal pathogen that causes yeast infections, thrush, and most dangerously, in immunocompromised individuals, sepsis. Understanding the function of genes that regulate thiamine synthesis provides an appealing entry into designing antifungal medications against C. glabrata. Preventing C. glabrata growth by starving it of thiamine may help the 30% of individuals with systemic Candidiasis do not survive the fungal infection. Ms. Lang’s detailed study of the evolution of function of Pdc2 in these two yeast species, in addition to four other species will provide important new insights into antifungal drug research development. Ms. Lang will be determining which species’ Pdc2 are capable of performing the function of inducing the transcription of thiamine synthesis genes and which are capable of inducing the critical sugar breakdown genes. She will then use a mutant screen to attempt to convert the C. glabrata Pdc2 into a transcription factor that now regulates sugar breakdown genes as well. Ms. Lang’s work will identify how the specificity of Pdc2 has evolved over time and should clarify the role of Pdc2 in metabolism in C. glabrata.