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Hypoxia 2009 Speakers
Gabriel Haddad
Professor of Pediatrics and Neuroscience, Chairman, Department of Pediatrics,University of California San Diego
Email: ghaddad@ucsd.edu
Talk Title: Selection for hypoxia tolerance in Drosophila
Session: Hypoxic Responses: Insights from Insects
Abstract: Hypoxia, as a result of disease or high altitude, can have devastating effects. Over the past decade, research in this area has begun to focus on the molecular and genetic mechanisms underlying hypoxic tissue injury or tolerance using different animal models. Some of studies also have explored strategies by which injury could either be prevented or alleviated and tolerance enhanced. The discovery of the hypoxia-inducible-factor (HIF) and its regulation during low O2 conditions in vertebrates and invertebrates has opened major avenues for investigating mechanisms of adaptation and potential strategies for therapy. However, there are mechanisms of hypoxia resistance or adaptation that are not related to HIF function but these genes are, by and large, unknown. We have used long-term experimental selection over many generations to obtain Drosophila melanogaster strains that can live perpetually in extremely low, normally lethal O2 conditions (4-5% O2). These strains show a dramatic phenotypic divergence from control animals, including a decreased recovery time after anoxia, a higher rate of O2 consumption in hypoxic conditions, and a decrease in body mass due to both decreased cell proliferation and cell size. We used gene expression profiling to identify altered transcript levels in the adapted flies and we show that mutations in many of the corresponding genes confer the ability to survive under extremely low O2 conditions.

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