Extreme oxygen deprivation is central to the pathology of several diseases involving cardiac and pulmonary dysfunction. Oxygen deprivation also plays a role in the resistance of solid tumors to radiation or chemotherapy treatment. Understanding the genetic and cellular response oxygen-deprivation resistant organisms have to anoxia, hypoxia will facilitate the development of treatment for the rescue of damaged ischemic tissue, or the destruction of oxygen deprived tumor cells. We found that the nematode C. elegans is capable of surviving prolonged exposure to anoxia (<.001 kPa Oxygen). Embryos exposed to anoxia leads to a complete arrest of cell cycle and developmental progression. Upon reexposure to oxygen, these processes are resumed. The long-term goal of this research is to characterize the molecular and cellular responses nematodes have to oxygen deprivation. The central hypothesis of this application is that embryos contain a genetic program to coordinate the arrest of biological processes such as cell division in response to anoxia. Previously, we found that the spindle checkpoint is required for embryos to arrest blastomeres in metaphase during exposure to anoxia. We will use a combination of genetic and cell biological techniques to further investigate the pathway between oxygen deprivation and cell division arrest in the nematode embryo by pursuing the following aims.
Aim 1. Examine the response the spindle checkpoint components have in embryos exposed to anoxia. Previously we found that the spindle checkpoint components (san-1 and mdf-2) are required for embryos to survive anoxia. We will use genetic and cell biological techniques to expand on this finding.
Aim 2. Use RNA interference to identify genes that are not required for embryo development, but are required for embryos to survive anoxia. Cell biological techniques will be used to determine if these gene products are required for blastomeres to arrest the cell cycle in response to anoxia.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM069419-01A1
Application #
6823828
Study Section
Genetics Study Section (GEN)
Program Officer
Anderson, James J
Project Start
2004-09-01
Project End
2009-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$171,737
Indirect Cost
Name
University of North Texas
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
614168995
City
Denton
State
TX
Country
United States
Zip Code
76203