Genetic Characterization of UTH1 and BXI1, Two Genes Involved in Yeast Programmed Cell Death (2009 - Present)

Investigator:  Nicanor Austriaco, Providence College
Mentor:  Brian Kennedy, University of Washington School of Medicine 

Abstract:  Apoptosis is both an important physiological process and a significant anti-tumor defense mechanism in multicellular organisms. Cells that bypass apoptosis in response to oncogenic stimuli can undergo malignant transformation. Some have even called the ability to evade programmed cell death a “hallmark of cancer”.  Significantly, there is good evidence that apoptosis contributes to the anti-tumor activity of many chemotherapeutic drugs and that mutations that disable apoptosis can result in multi-drug resistance. The budding yeast, Saccharomyces cerevisiae, has served as a useful model for complex physiological processes of metazoan cells including apoptosis.

Much work has gone into attempting to describe the molecular mechanisms that drive each process.  For the past three years, my laboratory at Providence College has studied UTH1 and BXI1, two genes linked with programmed cell death in yeast.  We have generated mutants lacking UTH1 and BXI1 and showed that they have phenotypes linking them to the oxidative stress response and the unfolded protein response respectively. This proposal outlines genetic strategies to identify the molecular pathways involved in UTH1 and BXI1 function.  It will exploit 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.