Insulin secretion and control of body size: The mechanisms regulating insulin secretion are highly conserved among animals. Just like mammals, insulin plays a critical role in the regulation of metabolism in Drosophila. However, insulin also directly regulates animal body size in flies, akin to insulin-like growth factor (IGF) in mammals. As a result, flies with defective insulin secretion are dramatically smaller than their wild-type counterparts. Using forward genetics, we have identified several novel and conserved regulators of animal body size, many of which may be important for type 2 diabetes in humans. We are now using genetic and cell biology approaches to functionally characterize these newly-identified regulators of insulin secretion.
Developmental control of regulated exocytosis: Regulated exocytosis is a fundamental cell biological process that releases specific cargoes to the extracellular environment in a stimulus-dependent manner. Importantly, dysregulation of this process underlies many human diseases, including endocrine disorders like diabetes and exocrine disorders like asthma and respiratory distress syndrome. Our experimental model system is the Drosophila larval salivary gland, which utilizes regulated exocytosis to secrete mucin-like “glue” proteins at the onset of metamorphosis. Salivary glands are composed of large cells that produce glue-containing secretory granules which are several micrometers in diameter, providing an ideal in vivo context to identify and characterize new proteins that play a role in regulated exocytosis. We have identified new and unexpected regulators of intracellular trafficking, and we are focused on understanding how these proteins impact the regulated exocytosis pathway.
Genetic and hormonal control of metamorphosis: The process of transforming a juvenile larva into a mature adult fly is remarkably complex; nearly every tissue present in the larval organism is dismantled and rebuilt or remodeled. However, the mechanisms that regulate this rebuilding of the organism remain unknown, providing an ideal opportunity to uncover new biological processes. One of the critical regulators of metamorphosis is the steroid hormone ecdysone. Systemic pulses of ecdysone direct developmental progression and trigger tissue remodeling during metamorphosis. Our lab has a large, unique collection of metamorphosis-specific lethal mutations derived from a forward genetic screen. We are using these mutations to genetically dissect ecdysone signaling as well as the biological processes that ecdysone coordinates during metamorphosis.