Michelle Mondoux

Research 

Energy homeostasis is crucial for survival. Nutrition influences fertility, lifespan, and other fundamental processes. Although the cellular and genetic responses to starvation have been well studied, the response to excess nutrition—or “nutrient stress”—is poorly understood. My lab uses the nematode Caenorhabditis elegans (“the worm”) as a model system to study the molecular, cellular, and genetic responses to glucose stress. 

Research in the lab is divided into two broad projects. The first involves characterizing pathways that are known to respond to glucose. I have identified three genes that are necessary for the glucose stress response: the insulin receptor (daf-2 in the worm), the O- GlcNAc transferase (ogt-1) and the O-GlcNAc’ase (oga-1). O-GlcNAc is a post-translational modification derived from glucose, and OGA-1 is a type II diabetes susceptibility locus in humans. OGA-1, OGT-1, and the insulin receptor are essential in mammals but can be studied with temperature-sensitive mutations or knockouts in the worm. Using genetics, molecular biology, and cell biology techniques, we will try to understand how these genes regulate fertility under glucose stress, and whether maternal glucose stress affects subsequent generations. 

The second project takes an unbiased approach to identify new genes that connect insulin signaling and glucose stress. Using a daf-2 mutant, I screened an RNAi knockdown library to find genes that decreased insulin signaling in the presence of glucose stress. I identified over 100 candidate genes that are known to be involved in processes including aging, the immune response, protein trafficking, and mitochondrial function. Future projects will determine which of these genes are required for the glucose stress response and elucidate how they regulate insulin signaling.