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Genetic and Molecular Analysis of Aging and Apoptosis in the Yeast,
Saccharomyces (2005 - Present)
Investigator:
Nicanor Austriaco,
Providence
College
Mentor: Brian Kennedy,
University of Washington School of Medicine
Abstract: Cellular aging and apoptosis are two cellular processes that
have been implicated in human disease. For instance, it is now clear
that both are potent anti-cancer mechanisms. Cells that either escape
senescence or 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 senescence and apoptosis contribute 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 aging
and apoptotic cell death. Molecular mechanisms of both these processes
appear to be conserved and genetic determinants have been identified in
yeast with orthologues in higher organisms. Much work has gone into
attempting to describe the molecular mechanisms that drive each
process. This research program outlines several genetic strategies to
identify molecular links between these two processes in yeast, links
that could be conserved in higher organisms. It will exploit the
primary advantage of the yeast system over its mammalian counterpart as
a model system for aging – simply, yeast cells are easier to work with
because they age and reach senescence within a matter of weeks.
Mammalian cells, on the other hand, take months to undergo senescence,
while mammalian organisms take years, if not decades, to age.
Specifically, this research program will determine if yeast cells that
undergo both replicative and chronological aging activate the apoptotic
pathway in order to die, by examining the lifespan of yeast cells
bearing gain-of-function and loss-of-function mutations in key yeast
apoptosis genes. It will also determine if the yeast cells undergoing
senescence from the accumulation of extrachromosomal circles activate
the apoptotic machinery to die. Finally, it will determine if the
chronological aging process that can be delayed by calorie restriction
(CR) functions through the apoptotic pathway by studying the effects of
CR on yeast cells bearing loss-of-function mutations in key yeast
apoptosis genes.
Presentations
2008 - 2009
Roussel, B., Austriaco, N. 2008. The
chemotherapeutic agent sulforaphane induces autophagy in the yeast,
Saccharomyces cerevisiae. Eastern Colleges Science Conference, Niagara,
NY, April 12.
Malouin, J., Di Raimo,
A., Austriaco, N. 2008. Yeast Bax inhibitor-1 is involved in the unfolded
protein response. Eastern Colleges Science Conference, Niagara, NY, April
12.
Goodwin, M.J.,
Austriaco, N. 2008. Characterization of the autophagy gene, ATG16, in a
Saccharomyces cerevisiae model of Crohn’s disease. Eastern Colleges
Science Conference, Niagara, NY, April 12.
Malouin, J., Di Raimo,
A., Austriaco, N. 2008. Yeast Bax inhibitor-1 is involved in the unfolded
protein response. 6th International Meeting on Yeast Apoptosis, Leuven,
Belgium, April 30-May 4.
Ritch, J.J., Sheehan, J.J.,
Austriaco, N. 2008. Characterization of the aging gene, UTH1, in the
yeast, Saccharomyces. 6th International Meeting on Yeast Apoptosis, Leuven,
Belgium, April 30-May 4.
Loudin, M.G., Austriaco,
N. 2008. Deleting UTH1 enhances yeast mitophagy and increases cell
viability during sugar-induced cell death in an AUP1-dependent manner. 6th
International Meeting on Yeast Apoptosis, Leuven, Belgium, April 30-May 4.
Roussel, B., Austriaco,
N. 2008. The chemotherapeutic agent sulforaphane induces autophagy in the
yeast, Saccharomyces cerevisiae. 3rd Annual Biology New England South
Meeting, Bristol, RI, December 2.
Gravel, E.S., Goodwin, M.J.,
Austriaco, N. 2008. Characterization of the autophagy gene, ATG16,
in a Saccharomyces cerevisiae model of Crohn’s disease. 3rd Annual Biology
New England South Meeting, Bristol, RI, December 2.
Feeley, E., Austriaco,
N. 2008. Screening for Bax inhibitor-1 (Bxi1p) interacting proteins using
the yeast two-hybrid system. Sigma Xi Annual Meeting and Student Research
Conference, Washington, DC, November 20-23.
Malouin, J.K.,
Austriaco, N. 2008. Yeast Bax-inhibitor (BXI1) regulates apoptosis
through the unfolded protein response. 3rd Annual Biology New England
South Meeting, Bristol, RI, December 2.
Cao, Y., Austriaco, N.
2008. Characterizing the responses of different cell types of the yeast Saccharomyces cerevisiae to ethanol-induced program cell death. 3rd Annual
Biology New England South Meeting, Bristol, RI, December 2.
Roussel, B., Austriaco,
N. 2008. The chemotherapeutic agent sulforaphane induces autophagy in the
yeast, Saccharomyces cerevisiae. 48th Annual Meeting of the American
Society for Cell Biology, San Francisco, CA, December 13-17.
Malouin, J.K., Austriaco, N. 2008. Yeast Bax-inhibitor (BXI1) regulates apoptosis
through the unfolded protein response. 48th Annual Meeting of the American
Society for Cell Biology, San Francisco, CA, December 13-17.
2007
- 2008 Ritch,
J.J., Sheehan, J.J., Goodwin, M.J., Austriaco, N. 2007. Characterization
of the aging gene, UTH1, in the yeast, Saccharomyces. Eastern Colleges
Science Conference, New York, NY, April 21.
Loudin, M.G., Austriaco,
N. 2007. Role of mitophagy in sugar induced cell death in the yeast,
Saccharomyces cerevisiae. 2nd BioNESUR Conference, Bristol, RI, November
30.
Roussel, B.N., Hittinger,
T.L., Fay, D., Austriaco, N. 2007. Genetic characterization of the
mechanism of action of sulforaphane (SFN) in the yeast, Saccharomyces.
Eastern Colleges Science Conference, New York, NY, April 21.
Pietrantonio, J.B., Austriaco, N. 2007. Induction of rapamycin-induced
cell death by Resveratrol in the yeast, Saccharomyces. 2nd Northeast
Regional IDeA Meeting, Burlington, VT, August 15-17.
Feeley, E., Malouin J.K.,
Austriaco, N. 2007. Characterization of the anti-apoptotic gene, Bax
inhibitor-1 (BXI1), in the yeast, Saccharomyces. Eastern Colleges Science
Conference, New York, NY, April 21.
Gittings, D.J., Loudin,
M.G., Austriaco, N. 2007. Genetic characterization of sugar-induced cell
death (SICD) in the yeast, Saccharomyces cerevisiae. 2nd Northeast
Regional IDeA Meeting, Burlington, VT, August 15-17.
Gittings, D.J., Loudin,
M.G., Austriaco, N. 2007. Genetic characterization of sugar-induced cell
death (SICD) in the yeast, Saccharomyces cerevisiae. 2nd
BioNESUR Conference, Bristol, RI, November 30.
Roussel,
R., Fay, D., Austriaco, N. 2007. Genetic characterization of the
mechanism of action of sulforaphane (SFN) in the yeast, Saccharomyces. 2nd
Northeast Regional IDeA Meeting, Burlington, VT, August 15-17.
Malouin, J., DiRaimo A.,
Austriaco, N. 2007. Yeast Bax inhibitor-1 (BXI1) is involved in the
unfolded protein response. 2nd BioNESUR Conference, Bristol, RI, November
30.
Davidson, S.M., Pinches,
N., Austriaco, N. 2007. Genetic characterization of acetic acid-induced
cell death in Saccharomyces cerevisiae. 2nd Northeast Regional IDeA
Meeting, Burlington, VT, August 15-17.
Contuzzi, G., Pilsmaker,
C.D., Ritch, J.J., Austriaco, N. 2007. Characterizating the apoptosis
pathway in yeast cells over-expressing mammalian Bax. 2nd BioNESUR
Conference, Bristol, RI, November 30.
Feeley, E., Austriaco,
N. 2007. Screening for Bax inhibitor-1 (Bxi1p) interacting proteins using
the yeast two-hybrid system. 2nd BioNESUR Conference, Bristol, RI,
November 30.
Loudin, M., Austriaco,
N. 2007. Characterization of sugar induced cell death (SICD) in the yeast,
Saccharomyces cerevisiae. Eastern Colleges Science Conference, New York,
NY, April 21.
Davidson, S.M., Pinches,
N., Austriaco, N. 2007. Genetic characterization of acetic acid-induced
cell death in Saccharomyces cerevisiae. 2nd BioNESUR Conference, Bristol,
RI, November 30.
Sheehan, J.J, Austriaco,
N. 2007. Characterization of the human aging gene, klotho, in the yeast,
Saccharomyces. 2nd BioNESUR Conference, Bristol, RI, November 30.
Malouin
J.K., Austriaco, N. 2007. Characterization of the anti-apoptotic
gene, Bax inhibitor-1 (BXI1), in the yeast, Saccharomyces. Posters on the
Hill, Washington, DC, April 25.
2006
- 2007
Sheehan, J., Alberts, C., Crowe, J., Luft, C., Roussel, B., Austriaco, N.
2006. Genetic characterization of the aging gene, UTH1, in the yeast Saccharomyces. Eastern Colleges Science/Sigma Xi Research Conference,
Philadelphia, PA, April 21-22.
Malouin, J., Ritch, J.J.,
Roussel, B., Sheehan, J., Austriaco, N. 2006. Genetic characterization of
the anti-apoptotic gene, BXI1, and the aging gene, UTH1, in the yeast, Saccharomyces. 1st Biennial National IDeA Symposium of Biomedical Research
Excellence (NISBRE), Washington, DC, July 20-22.
Ritch, J.J., Sheehan, J.,
Loudin, M., Austriaco, N. 2006. Genetic characterization of the aging
gene, UTH1, in the yeast, Saccharomyces. Cold Spring Harbor Laboratory
Molecular Genetics of Aging Meeting, Cold Spring Harbor, NY, October 4-8.
Malouin, J., Austriaco,
N. 2006. Genetic characterization of the anti-apoptotic gene, BXI1, in
the yeast Saccharomyces. Eastern Colleges Science/Sigma Xi Research
Conference, Philadelphia, PA, April 21-22. |
