Genetic dissection of motivational drive to eat

项目摘要 食物摄入不仅可以由对卡路里的需求引发，还可以由对特定营养素的需求引发， 或需求独立的机制。近几十年来的研究取得了实质性进展， 我们对能量稳态背景下控制食物摄入的神经通路的理解。在 与此相反，对不依赖热量的喂养的机制仍然知之甚少。使用 果蝇作为一个模型系统，我最近确定并表征了第一个神经回路编码 蛋白质特异性饥饿在任何模型系统中。该电路为今后的研究提供了新的途径 转化为与热量需求无关的营养素特定食物摄入。在这项研究中，我将 表征介导蛋白质稳态调节的分子和细胞底物 消费，特别关注蛋白质丰度或稀缺性的感测。我们还计划 阐明环境蓝光如何在缺乏营养需求的情况下驱动摄食行为。到 为了实现这些目标，我们将采用多学科的方法，包括大规模的基因工程。 分析，定量行为测量，免疫组织化学，功能成像，贴片- 钳位电生理学和代谢组学分析。这些调查将大大 加深我们对不依赖卡路里的进食动机的理解， 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.