Grant: Discovery Grants Program - Individual

In order to maintain nutrient homeostasis, animals must have robust systems to control nutrient intake. For example, the sense of taste plays an important role in identifying nutrients for consumption. However, mounting evidence suggests that animals also use taste-independent mechanisms to detect specific nutrients following ingestion and guide their feeding behavior. We and others have recently demonstrated that flies use post-ingestive sensors to adjust their feeding decisions according to the nutritive value of specific sugars. The long-term goal of my proposed Discovery Grant research program is to use the powerful molecular, genetic, and behavioral tools of the fruit fly, Drosophila melanogaster, to unravel the taste-independent neuronal mechanisms regulating intake of several key nutrients salt, amino acids, water, and fats.We have three specific aims for the next five years:Aim 1: To characterize the taste-independent impact of various nutrients on consumption and reward, and the dependence of these effects on prior nutrient deprivation. Using mutants lacking taste input, we will isolate the taste-independent component of preference for salt, amino acids, water, and fats. We will also use classical conditioning memory assays to assess the impact of each nutrient on brain reward systems.Aim 2: To uncover neuropeptidergic modulators of post-ingestive nutrient sensing mechanisms. Neuropeptides are known to play important roles in linking internal states and behavior. We will use neuronal silencing and RNA-interference screens to identify and characterize neuropeptides regulating the consumption of each key nutrient.Aim 3: To dissect the neural pathways linking taste-independent nutrient sensing with behavior. We will use genetically encoded neuronal silencers and activators to probe the function of specific neurons in nutrient seeking behavior. We will also use functional imaging and electrophysiology to characterize changes in the activity of those neurons following nutrient ingestion. The proposed research leverages the powerful fly genetic toolkit to understand the complex process of detecting ingested nutrients and then altering behavior to promote appropriate levels of intake. This is a fundamental biological problem that will provide insight into how neural circuits process sensory information, how information processing is affected by internal metabolic states, and how behavior is controlled on short- and long-term time scales. In addition to advancing knowledge of brain function, our research on the mechanisms regulating insect feeding will have important applications in pest control, which profoundly impacts the economy and environment in Canada and around the world.