A Drosophila Model for the Regulation of Aerobic Glycolysis

项目摘要 Tennessen实验室使用果蝇作为模型来了解碳水化合物 代谢支持动物生长和发育的生物合成和能量需求。我们正在进行的 研究集中在称为瓦尔堡效应（有氧糖酵解）的代谢程序上。这个代谢程序 允许生长和增殖的细胞代谢大量的葡萄糖以产生生物质， 合成促生长信号分子。虽然有氧糖酵解通常与肿瘤有关， 在那里，它促进癌细胞、健康动物细胞如干细胞和激活的 T细胞也利用这种代谢程序来驱动生物合成并调节细胞命运决定。因此，基本 有氧糖酵解的研究不仅有可能确定可以靶向的代谢机制， 不仅能抑制肿瘤生长，还能揭示健康细胞如何操纵糖酵解代谢， 支持正常的发育生长。我发现果蝇也用 有氧糖酵解促进生长，并建立了苍蝇作为模型系统，用于研究遗传 调节这种代谢程序的机制。研究新陈代谢的一个重要工具是呼吸测定法， 其提供氧气消耗和二氧化碳产生的测量。这些测量， 当与代谢组学方法结合使用时，对于理解糖酵解通量如何 在快速生长的动物组织中，生物合成和能量生产之间保持平衡。然而，准确 小动物如果蝇的呼吸测定法测量需要专门的仪器。在这 建议，我要求资金购买紫貂系统昆虫呼吸测定系统，能够 测量每只果蝇的耗氧量和二氧化碳产量。我们之前 使用合作者系统进行我们的呼吸测量研究，然而，该系统不再适用于 使用我的实验室。本提案中描述的Sable Systems昆虫呼吸测定系统将显著 增强我们研究有氧糖酵解如何促进果蝇幼虫快速生长的能力。

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.