Genetic analysis of AMPK function in Drosophila

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DESCRIPTION (provided by applicant): Eukaryotes tolerate fluctuations in the environmental supply of nutrients and their consumption by cellular metabolism by suspending anabolic processes and utilizing stored energy. From yeast to mammals, the AMP-activated kinase (AMPK) serves as the sensor of cellular energy stores and the activator of metabolic switches that conserve ATP. While the key role of AMPK in directing cellular metabolism is well established, little is known about the upstream regulators and downstream effectors of AMPK signaling. The goal of these studies is to use a genetic approach in Drosophila to identify novel components of the AMPK signaling pathway. In specific aim 1, I will determine the growth and metabolic phenotypes resulting from loss- and gain-of-function of AMPK. In specific aim 2, I will perform genetic and biochemical analyses to confirm relationships between AMPK and its putative upstream regulators and downstream substrates. In specific aim 3, I will undertake a genetic screen for suppressors and enhancers of AMPK mutant phenotypes to discover novel components of the AMPK signaling pathway. Collectively, these studies should shed light on an important pathway that has resisted characterization using biochemical approaches.