Identification of Genes as Novel Potential Therapeutic Targets for Type II Diabetes (2010)

Undergraduate: Lu Liu

Faculty Advisor: Jay Brenman
Department: Biology

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AMP-activated protein kinase (AMPK) is a highly conserved energy sensor in eukaryotes that monitors cellular metabolism. Therefore, it is an exciting new drug target for chronic metabolic diseases, specifically type II diabetes. The activation of AMPK increases ATP production via the up-regulation of glycolysis and other energy-generation pathways along with a concomitant decrease in fatty acid and cholesterol synthesis. Most importantly, commonly prescribed drugs for type II diabetes, such as metformin, activate AMPK. However, most of these drugs suffer from inadequate efficacy and durability and other dangerous side effects. The principle aim of my study is to identify novel genes involved in the AMPK signaling pathway through a forward genetic modifier screen in Drosophila melanogaster. We are employing EMS to induce mutations in the germ-line of male flies. Complete loss, or knockdown, of AMPK results in severe phenotypes and lethality at the whole organism level. Any genetic modification induced by EMS capable of suppressing this lethality, i.e., rescuing the knockdown, is vital to better understanding the AMPK signaling pathway. Their progeny were scored for rescue phenotypes and they were retested for rescue a second time to validate the rescue. Currently we have isolated and validated five separate EMS mutagenized fly lines capable of suppressing the lethality of AMPK knockdown. Each fly line has been propagated as a stock and will be further characterized and mapped.