Was and Undergraduate Researcher
Is a Medical Student at Washington University (class of 2006)
Howard Hughes Medical Institute Symposium Abstract
DEVLOPMENT OF A PROTOCOL FOR HYPOXIA RESISTANCE SCREENING AND RESULTS. Michael Bottros1, C. Michael Crowder2. Biology Department, Washington University, St. Louis, MO1; Departments of Anesthesiology and Molecular Biology/Pharmacology, Washington University Medical School, St. Louis, MO2.
Hypoxic cell death is a very important issue. Heart attacks and strokes are the result of hypoxic cell death. Until recently, there were no model systems amenable to forward genetics where mutants have been isolated which are resistant to hypoxia. The Crowder lab has found that mutations in the insulin receptor binding daf-2 prevent hypoxic death in C. elegans (manuscript submitted). Thus, hypoxic death can be blocked by single gene mutations.
I have been working in Dr. Crowder's laboratory to screen for new C. elegans mutants that are resistant to hypoxia. Once a method for screening was perfected, we performed mutagenesis screens to find C. elegans resistant to hypoxia. We have screened through 8,758 mutagenized genomes and found 400 mutants that were potentially resistant to hypoxic death. Of those 400 mutants, only 67 produced progeny to be tested for secondary screens. Eighteen lines display varying levels of hypoxia resistance after repeated testing. Whereas 0% wild-type N2 survive, 5%-50% of these mutagenized worms survive. We will now map and identify the mutant genes producing the hypoxia resistance. Identification of these genes will help in understanding the mechanisms underlying hypoxic cell death and potentially help in development of novel strategies for the treatment of heart attacks and strokes.