Project Summary Food intake can be triggered by not only the need for calories, but also the need for specific nutrients, or need-independent mechanisms. Studies over the recent decades have made substantial progress in our understanding of neural pathways controlling food intake in the context of energy homeostasis. In contrast, mechanisms underlying calorie-independent feeding remain poorly understood. Using Drosophila as a model system, I recently identified and characterized the first neural circuit encoding protein-specific hunger in any model system. This circuit provides a novel entry for future investigations into the nutrient specific food intake that is independent of caloric needs. In this proposed study, I will characterize the molecular and cellular substrates mediating the homeostatic regulation of protein consumption, with a particular focus on the sensing of protein abundance or scarcity. We also plan to elucidate how environmental blue light drives feeding behavior in the absence of nutritional needs. To achieve these goals, we will employ a multidisciplinary approach including large-scale genetic analyses, quantitative behavioral measurements, immunohistochemistry, functional imaging, patch- clamp electrophysiology and metabolomics analysis. Together these investigations will substantially deepen our understanding of calorie-independent motivational drive to eat, shedding light on the fundamental principles for the organization and modulation of feeding behaviors.