Program in Neuroscience

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Both cancer cells and embryonic stem cells rely on a specialized metabolic program known as aerobic glycolysis to support their rapid proliferation. Aerobic glycolysis, which is also known as the Warburg effect in the context of tumor metabolism, is characterized by the increased expression of glucose transporters, enzymes involved in glycolysis, and other proteins that promote glycolytic flux. This up-regulation of glycolysis, however, is not solely used to produce energy. Instead, the abundant supply of glucose-derived metabolites is used to generate the amino acids, nucleotides, and fatty acids required for rapid proliferation. Meanwhile, a significant quantity of the pyruvate generated during this process is not oxidized in the mitochondria, but rather is converted into lactate—a hallmark of aerobic glycolysis that is required for maximal glycolytic flux.

The manner in which rapid cell proliferation relies on aerobic glycolysis suggests that understanding the molecular mechanisms regulating this metabolic program could lead to new cancer therapies, as well as advances in the field of stem cell biology. Toward this goal, several groups are using mammalian cell culture to study aerobic glycolysis. There is still a significant need, however, for model systems with which to explore how cells initiate aerobic glycolysis in vivo. In order to fill this void, my lab is using the fruit fly Drosophila melanogaster as a genetic model to study aerobic glycolysis.

All growth during the Drosophila life cycle is restricted to the larval stage, when animals increase their body size approximately 200-fold over the course of four days. This growth phase is preceded by a dramatic metabolic switch, which induces the coordinate expression of nearly every gene involved in glycolysis and lactate production. The resulting metabolic program displays the central hallmarks of aerobic glycolysis, indicating that like cancer cells, growing larvae use this metabolic program to efficiently derive biomass from carbohydrates. My lab is exploiting this discovery to determine how aerobic glycolysis is regulated in the context of normal animal growth and physiology.