Received December 9, 2005
Revised December 19, 2005
Accepted after revision January 16, 2006

¹ University of California, San Diego

^* To whom correspondence should be addressed. E-mail: ghaddad{at}ucsd.edu.

	Abstract

There have been extensive studies and experiments on cells, tissues and animals that are susceptible to low O2 and many pathways have been discovered that can lead to injury in mammalian tissues. But other pathways that can help in the survival to low O2 have also been discovered in these same tissues. However, it should be noted that the mechanisms that can lead to better survival in susceptible mammalian tissues have quantitatively a "narrow range" for recovery since these tissues are inherently at risk. Another strategy to understand the susceptibility of organisms is to learn about pathways used by anoxia-resistant animals. Approximately a decade ago, we discovered that one such animal, Drosophila melanogaster, is very tolerant. Here, we detail some of the studies that we performed and the strategies that we developed to understand the mechanisms that underlie their fascinating resistance to measured PO2 of zero! We employ three ideas to try to address our questions: 1) mutagenesis screens to identify loss-of-function mutants, 2) microarrays on adapted versus naïve flies and 3) studying cell biology and physiology of genes that seem important in flies and mammals. The hope is to learn from these studies about the fundamental basis of tolerance to the lack of O2, and with this knowledge be able to develop better therapies for the future.

Key Words: Hypoxia, Neuroscience, Oxygen