Research Projects

This project aims to understand how conserved metabolic events orchestrate fungal morphogenesis in response to nutrient fluctuations. The fungal model system, Saccharomyces cerevisiae, exhibits reversible fungal morphogenesis, including dimorphic switching between yeast cells and pseudohyphal cells when nutrient levels fluctuate. Pseudohyphae are elongated and exhibit altered cell polarity and cell adhesion compared to yeast cells, resulting in an extensive and invasive network of cells. Nitrogen limitation is a key trigger for pseudohyphal differentiation in S. cerevisiae, but other metabolic drivers critical for this dimorphic transition remain to be elucidated. Preliminary data shows that glucose positively influences pseudohyphal differentiation in a concentration-dependent manner, and the ability of yeast cells to metabolize glucose is critical for pseudohyphal differentiation. Specific aims include identifying the glucose-dependent central carbon metabolic pathways driving pseudohyphal differentiation, and elucidating the mechanisms by which glucose regulates pseudohyphal differentiation. Comparative RNA-Seq analysis and targeted mass spectrometry using wild-type and glycolysis/PPP knockout strains grown in nitrogen-limiting/glucose rich conditions in the presence and absence of glucose metabolism inhibitors will provide a systems-level understanding of the influence of glucose during pseudohyphal differentiation and provide insights into the putative mechanisms underlying glucose mediate regulation of pseudohyphal differentiation. Given that fungal morphogenesis and glucose metabolism are highly conserved across multiple fungal species, knowledge gained from this proposal can be broadly applied to gain fundamental insights about how this phenomenon is regulated across multiple fungal systems.