A Drosophila Model for the Regulation of Aerobic Glycolysis

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Project Summary The Tennessen Lab uses the fruit fly, Drosophila melanogaster, as a model to understand how carbohydrate metabolism supports the biosynthetic and energetic demands of animal growth and development. Our ongoing studies focus on a metabolic program known as the Warburg effect (aerobic glycolysis). This metabolic program allows growing and proliferating cells to metabolize large quantities of glucose in order to generate biomass and synthesize pro-growth signaling molecules. While aerobic glycolysis is most commonly associated with tumors, where it promotes the growth and survival of cancer cells, healthy animal cells, such as stem cells and activated T cells, also use this metabolic program to drive biosynthesis and regulate cell fate decisions. Therefore, basic studies of aerobic glycolysis have the potential to not only identify metabolic mechanisms that could be targeted to inhibit tumor growth but also to reveal how healthy cells manipulate glycolytic metabolism as a means of supporting normal developmental growth. I have discovered that the fruit fly Drosophila melanogaster also uses aerobic glycolysis to promote growth and have established the fly as a model system for studying the genetic mechanisms that regulate this metabolic program. An essential tool for studying metabolism is respirometry, which provides measurements of oxygen consumption and carbon dioxide production. These measurements, when used in combination with metabolomics approaches, are essential for understanding how glycolytic flux is balanced between biosynthesis and energy production in rapidly growing animal tissues. However, accurate respirometry measurements in small animals such as fruit flies require specialized instrumentation. In this proposal, I am requesting funds to purchase a Sable Systems Insect Respirometry System that is capable of measuring both oxygen consumption and carbon dioxide production from individual fruit flies. We previously used a collaborators system to conduct our respirometry studies, however, this system is no longer available for use by my lab. The Sable Systems Insect Respirometry System described in this proposal will significantly enhance our ability to study how aerobic glycolysis promotes rapid growth in Drosophila larvae.