The Role of Serotonin in Energy Homeostasis in C. elegans

描述(由申请人提供)： 为了确保生存，动物必须不断评估环境中的食物状况，并通过将食物摄入量与能量消耗相匹配来做出适当的反应。两者之间的净平衡反映在动物的脂肪储备中。神经递质5-羟色胺在维持这种动态平衡中起着核心作用，它通过传递来自环境的食物信号来引起动物行为和生理的变化，从而维持脂肪的动态平衡。这项研究的目的是解决这个问题：“血清素信号是如何调节线虫体内的能量平衡的？”我已经确定了几个对线虫体内5-羟色胺脂肪调节至关重要的关键基因。我将结合行为和生理分析，研究这些新发现的基因在食物摄入量和能量消耗中的作用。结合分子和遗传分析，我的目标是明确线虫的5-羟色胺能网络，该网络将食物感觉与摄食调节和能量消耗的变化联系在一起。我目前的研究目标与我在了解环境如何在生物体水平上影响复杂的行为和生理的长期兴趣很好地一致。了解遗传学和环境的复杂交集是生物科学的前沿，对人类健康有重大的直接影响。这里提出的工作为我在接下来的两年里作为一名学术研究机构的独立研究员奠定了基础。我目前在加州大学旧金山分校的环境，在Kaveh Ashrafi博士和Keith Yamamoto博士的指导下，非常适合我的科学和专业兴趣。能源平衡的放松导致肥胖，这是一个日益严重的全球健康问题。事实上，目前的估计表明，超过30%的美国人患有肥胖症，这是心血管疾病、糖尿病和预期寿命缩短的主要风险因素。在包括老鼠和人类在内的许多物种中，5-羟色胺功能的古老保守表明，这里提出的工作将为研究身体脂肪调节提供新的遗传靶点。

DESCRIPTION (provided by applicant): To ensure survival, animals must constantly assess food status in the environment, and respond appropriately by matching food intake to energy expenditure. The net balance between the two is reflected in the fat stores of the animal. The neurotransmitter serotonin plays a central role in maintaining this dynamic balance, by relaying food signals from the environment to elicit changes in behavior and physiology of the animal so that fat homeostasis is maintained. The goal of the research proposed here is to address the question: "How does serotonin signaling modulate energy balance in C. elegans?" I have identified a few key genes that are important for serotonin fat regulation in C. elegans. Using a combination of behavioral and physiological assays, I will examine the roles of these newly-identified genes in food intake and energy expenditure. Together with molecular and genetic analyses, I aim to specify the serotonergic network that couples food sensation to changes in feeding regulation and energy expenditure in C. elegans. My current research objectives are well-aligned with my long-term interest in understanding how the environment influences complex behavior and physiology at the organismal level. Understanding the complex intersection of genetics and environment is a frontier in the biological sciences with major, direct impacts on human health. The work proposed here lays the foundation upon which I will embark as an independent investigator at an academic research institution in the next two years. My current environment at the University of California-San Francisco under the mentorship of Dr. Kaveh Ashrafi and Dr. Keith Yamamoto, is ideally suited for my scientific and professional interests. The de-regulation of energy balance leads to obesity, a rising health concern world-wide. Indeed, current estimates suggest that more than 30% of Americans are obese, a condition that is a prime risk factor for cardiovascular disease, diabetes and reduced life expectancy. The ancient conservation of serotonin function in many species including mice and humans suggests that work proposed here will provide novel genetic targets for the study of body fat regulation.