MODELING CELL DEATH AND HUMAN DISEASE IN THE BUDDING YEAST, SACCHAROMYCES CEREVISIAE
The budding yeast, Saccharomyces cerevisiae, has served as a useful model for complex physiological processes of metazoans. For the past fifteen years, our laboratory at Providence College has investigated the genetics of programmed cell death in budding yeast. We have also used this model organism to begin to understand how cell death is linked to disease.
First, we are investigating the molecular mechanism of Bax inhibitor function in cell death. Bax inhibitor was first identified as an oncogene that is upregulated in a variety of tumors. Structure function analysis suggests that Bax inhibitor is a calcium channel that defines the TMBIM family of proteins. Saccharomyces cerevisiae has one member of the TMBIM family, which we have named BXI1. Our studies suggest that Bxi1p is an ER-localized calcium eflux channel. We are continuing to characterize the function of this protein, both in yeast and in bacterial cells.
Second, we have recently begun to elucidate the mechanism of action of overexpressed alpha-synuclein, which is a protein found in toxic aggregates in the brains of Parkinson's patients. Using yeast cells developed by others to overexpress human alpha-synuclein in yeast, we are examining the effects of a panel of small molecules on the aggregation of this protein in eukaryotic cells.
Recently, in light of the global COVID-19 pandemic, the lab has pivoted some of its research capacity to try to develop a yeast-based vaccine delivery system using the human probiotic yeast, Saccharomyces boulardii.
Overall, our laboratory exploits the primary advantage of the yeast system over its mammalian counterpart as a model system for programmed cell death: Yeast cells are amenable to genetic analysis that allows investigators to identify rapidly molecular pathways underlying a biological process.
Saccharomyces cerevisiae cells stained with solophenyl flavine to visualize the chitin levels in their cell walls. Research in our lab suggests that cell wall integrity in yeast modulates the cell’s response to agents that induce programmed cell death. [Image taken by Shawn Davidson ’10]