Genetic dissection of motivational drive to eat

项目摘要 食物摄取不仅可以由卡路里需求引发，也可以由特定营养素需求引发， 或独立于需求的机制。近几十年来的研究在以下方面取得了实质性进展 在能量平衡的背景下，我们对控制食物摄入量的神经通路的理解。在……里面 相比之下，不依赖卡路里的喂养背后的机制仍然知之甚少。vbl.使用 以果蝇为模型系统，我最近发现并表征了第一个神经回路编码 在任何模型系统中都存在蛋白质特有的饥饿。该电路为今后的研究提供了一个新的入口 与卡路里需求无关的营养特定食物摄入量。在这项拟议的研究中，我将 表征介导蛋白质动态平衡调节的分子和细胞底物 消费，特别是对蛋白质丰度或稀缺性的感知。我们还计划 阐明在缺乏营养需求的情况下，环境蓝光如何驱动摄食行为。至 为了实现这些目标，我们将采用多学科方法，包括大规模遗传 分析，定量行为测量，免疫组织化学，功能成像，贴片- 钳夹电生理及代谢组学分析。这些调查加起来将在很大程度上 加深我们对不依赖卡路里的进食动机的理解，揭示 组织和调节摄食行为的基本原则。

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.