How does metabolic rate affect age-induced genomic instability?
Dan Gottschling, Full Member, Basic Sciences - FHCRC
Wayne Van Voorhies, Assistant Professor, Molecular Biology - NMSU
There are a myriad of hypothesis to explain the increased incidence of cancer with age. One of the major hypotheses suggests that high metabolic rate leads to increased cellular damage, including events that ultimately lead to cancer. The Gottschling lab discovered that as yeast cells age, they switch to a higher rate of genomic instability. We propose to use new methods developed in the Gottschling lab, to isolate old yeast mother cells (which are analogous to stem cells in metazoans) and measure their metabolic rate - using methods developed in the Van Voorhies lab. We will combine this analysis with genetic and physiological alterations to determine whether metabolic rate impacts age-induced genomic instability in old mother yeast cells. This study will address fundamental issues in eukaryotic cells that may explain age-dependent oncogenesis.
Specifically we propose to:
- Purify old mother cells for metabolic rate measures. The Gottschling lab has recently developed a genetic method to enrich for old mother yeast cells. We will now combine this method with physical isolation methods to purify mother cells of varying ages. These purified cells will be used for metabolic rate measurements.
- Measure metabolic rate in yeast cells as they age. Using methodologies developed and routinely used in the Van Voorhies lab, we will determine the metabolic rate of mother yeast cells as they age. We are particularly interested in whether metabolic rate changes correlate with the onset of LOH.
- Measure metabolic rate in mutant yeast cells as they age. The Gottschling lab has begun to identify mutations in yeast that change the onset of age-induced LOH or abolish it all together. The metabolic rate of these mutant yeast will be determined as a function of their age. Such an analysis will permit us to test whether metabolic rate does indeed affect age-induced LOH.
For More Information:
To learn more about the research talking place in Dr. Gottschling's lab, visit: labs.fhcrc.org/gottschling/
Information about Dr. Van Voorhies' research can be found at: http://research.nmsu.edu/molbio/VanVoorhies.html
Faculty and students interested in learning more about this pilot project may contact Dr. Dan Gottschling or Dr. Wayne Van Voorhies.