Eating and Sleeping: How neuronal SKN-1/Nrf regulates satiety using the worm C. elegans.

过度进食会导致严重的健康并发症。因此，了解饱腹感调节（何时停止进食）很重要。该项目的重点是这些生物决定如何工作，以便它们可以被利用来改善人类健康和健身。关于食物的信息是通过感觉神经系统获得的，并与来自身体的与饥饿或饱腹感有关的内部线索相结合。这些信号的整合控制食物摄入，维持体内平衡并预防疾病。我们在线虫C.它拥有完整的神经系统，并配备了强大的遗传、分子和行为工具。In C.在线虫中，化学感受神经元感知食物，并通过激素将信息传递给动物的其他部分，以控制行为和生理。我们的实验室发现，SKN-1，相当于哺乳动物Nrf的蠕虫，在两个ASI神经元中起作用，以感知食物和控制饱腹感。为了实现这一目标，SKN-1整合了胰岛素和TGF-β信号传导，并促进了能量稳态所需的强大线粒体网络。SKN-1也是一种特征良好的长寿基因（Tullet et et al，2008），由于食物摄入对疾病（例如糖尿病，心血管疾病）具有重大影响，通过研究SKN-1的神经作用，我们不仅可以确定其在食物相关行为中的作用，还可以确定食物相关行为，长寿和年龄相关健康之间的重要联系。该项目使用多种技术：遗传学，行为测定，分子生物学和各种显微镜（包括共聚焦和TEM），以深入研究所涉及的潜在遗传和生物过程。学生将绘制神经元回路，识别SKN-1的新型遗传相互作用，并充分探索破坏饱腹感的生理影响。由于Nrf在哺乳动物大脑中对调节食物相关行为很重要的区域中表达，因此该项目将为我们看待Nrf功能的方式提供一个步骤。

Over-eating can lead to serious health complications. So understanding satiety regulation (when to stop eating) is important. This project focuses on how these biological decisions work so that they can be harnessed to improve human health and fitness. Information on food is obtained via the sensory nervous system and integrates with internal cues from the body relating to hunger or satiety. Integration of these signals controls food intake, maintains homeostasis and prevents disease. We study this in the nematode worm C. elegans which have a fully mapped nervous system, and come complete with a selection of strong genetic, molecular and behavioural tools. In C. elegans, chemosensory neurons sense food and relay information to the rest of the animal via hormones to control behaviour and physiology. Our lab has found that SKN-1, the worm equivalent of mammalian Nrf, acts in two ASI neurons to sense food and control satiety. To achieve this SKN-1 integrates insulin and TGF-B signalling and promotes a robust mitochondrial network required for energy homeostasis. SKN-1 is also a well-characterised longevity gene (Tullet et al, 2008), and as food intake has massive implications for disease (e.g. diabetes, cardiovascular disease), via studying SKN-1's neurological role we will not only define its role in food-related behaviour but also important links between food-related behaviour, longevity, and agerelated health. This project uses a variety of techniques: genetics, behavioural assays, molecular biology, and a variety of microscopy (including confocal and TEM) to delve into the underlying genetic and biological processes involved. The student will map the neuronal circuits, identify novel genetic interactors of SKN-1, and fully explore the physiological effects of disrupted satiety. As Nrf is expressed in regions of the mammalian brain important for regulating food-related behaviour, this project will provide a step change in the way we view Nrf function.