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Genetic dissection of motivational drive to eat

$451,000R35FY2025GMNIH

University Of California, San Francisco, San Francisco CA

Investigators

Abstract

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 (e.g., hedonic factors, social experience, stress, etc.). 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, there is a profound gap in our understanding of mechanisms governing calorie-independent feeding. Using protein-specific appetite in Drosophila as a model system, our lab seeks to understand how specific nutritional needs and need- independent mechanisms give rise to appetites. In this proposed study, we will characterize the circuit and molecular substrates composing the negative feedback loop during the homeostatic regulation of protein specific appetite, as well as its coordination with other types of hunger. We also plan to investigate two aspects of need-independent mechanisms controlling feeding, including how blue light and social isolation impact food choice. To achieve these goals, we will employ a multidisciplinary approach including large-scale genetic analyses, quantitative behavioral measurements, immunohistochemistry, lipidomics analyses, stable isotope ratio mass spectrometry, functional imaging, and patch-clamp electrophysiology. 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.

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