Genetic Characterization of UTH1 and BXI1, Two Genes Involved in Yeast
Programmed Cell Death (2009 - Present)
Mentor: Brian Kennedy,
University of Washington School of Medicine
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.
The genetic strategies
described in this proposal will seek to clarify the genetic relationships
between UTH1, BXI1, and other apoptotic genes in yeast to identify the
molecular pathways that regulate programmed cell death in this organism.
Given the remarkable conservation of the apoptotic pathways across diverse
species, this analysis, which takes advantage of the genetic tools and
ease of study associated with the yeast system, should lead to further
insights into the analogous processes in higher organisms including human