Analysis of the Regulation of G protein-Coupled Sensory Signaling in C. Elegans

线虫 G 蛋白偶联感觉信号的调节分析

• 批准号: 0917896
• 负责人: Denise Ferkey
• 金额: $ 74.5万
• 依托单位: SUNY at Buffalo
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2013-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0917896&HistoricalAwards=false
• 关键词: Analysis; Regulation; protein; Coupled; Sensory

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).Intellectual MeritAll animals rely on their ability to sense and respond to their constantly changing environments to survive. Because they do not have eyes or ears, C. elegans (small roundworms) depend heavily upon their ability to taste and smell chemical information in their soil environment to find food and avoid danger; animals must move towards chemicals that indicate a food source while avoiding chemicals that indicate potentially harmful environments. These behavioral responses are elicited when the chemical signals (tastants and odorants) bind to proteins (receptors) on sensory nerve cells (neurons) and initiate a chain of intracellular events that ultimately activates the neuron. Neuronal activity, in turn, controls the behavior of the organism. Although this process of chemical signal transduction is highly conserved across species, there are still large gaps in our understanding of the mechanisms used to regulate signaling. Coupled with powerful genetic and molecular tools, C. elegans is an ideal model system in which to dissect the contributions of individual genes and regulatory pathways to integrated neuronal function and sensory behavior. Loss of a negative regulator of signaling (C. elegans GRK-2) surprisingly leads to decreased calcium signaling in sensory neurons and a concomitant loss of both attractive and avoidance chemosensory behaviors. In the absence of GRK-2 there appears to be an upregulation of compensatory inhibitory pathways that dampen signaling to protect neurons from overstimulation. This project will utilize cellular, biochemical and genetic approaches in a simple model organism to understand how cells respond to aberrant signaling; the findings will benefit researchers working in organisms ranging from yeast to humans. In particular, they will provide valuable information on the interconnectedness of signaling and regulatory pathways downstream of receptors. In addition, novel mechanisms used by cells to compensate for mis-regulated signaling may be revealed. Broader ImpactGraduate students and undergraduates, including women and minority students, will participate in these studies. The University at Buffalo (UB) is a very diverse campus, providing a great opportunity to mentor minority students. Funds from this grant will support a summer stipend for an undergraduate from a Liberal Arts College that does not itself have undergraduate research. Providing early exposure to hypothesis-driven research is essential for preparing students for careers in the biological sciences. Students will present their findings at local (monthly), regional and international meetings. Importantly, the annual C. elegans meetings foster the development of junior scientists because many of the speakers are selected from graduate student submitted abstracts. Findings from this work will also be included in the lectures in an undergraduate Signal Transduction course at UB. Mutants obtained from the genetic screens in this project will be deposited at the Caenorhabditis Genetics Center, which will distribute them to any investigator that requests them. New gene and phenotype descriptions will also be incorporated into Wormbase, an online open access resource.

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。智力功绩所有动物都依赖于它们感知和应对不断变化的环境的能力来生存。 因为他们没有眼睛和耳朵，C。线虫（小蛔虫）在很大程度上依赖于它们在土壤环境中品尝和闻到化学信息的能力来寻找食物和避免危险;动物必须向指示食物来源的化学物质移动，同时避免指示潜在有害环境的化学物质。 这些行为反应是在化学信号（促味剂和气味剂）与感觉神经细胞（神经元）上的蛋白质（受体）结合并启动最终激活神经元的细胞内事件链时引发的。 神经元的活动反过来又控制着生物体的行为。 尽管这种化学信号转导过程在物种间高度保守，但我们对用于调节信号传导的机制的理解仍然存在很大的差距。 再加上强大的遗传和分子工具，C。线虫是一个理想的模型系统，在其中剖析单个基因和调控途径对整合的神经元功能和感觉行为的贡献。 信号传导负调节因子的丧失（C. elegans GRK-2）令人惊讶地导致感觉神经元中钙信号传导的减少以及伴随的吸引和回避化学感觉行为的丧失。 在缺乏GRK-2的情况下，似乎存在补偿性抑制途径的上调，其抑制信号传导以保护神经元免受过度刺激。 该项目将在一个简单的模型生物中利用细胞、生物化学和遗传学方法来了解细胞如何对异常信号做出反应;这些发现将使从酵母到人类的生物研究人员受益。 特别是，它们将提供有关受体下游信号传导和调节途径相互联系的有价值的信息。 此外，细胞用于补偿错误调节信号的新机制可能会被揭示。 更广泛的影响研究生和本科生，包括妇女和少数民族学生，将参加这些研究。 布法罗大学（UB）是一个非常多元化的校园，为少数民族学生提供了很好的指导机会。 这笔赠款的资金将用于支持一所本身没有本科研究的文科学院的本科生的夏季津贴。 提供早期接触假设驱动的研究是必不可少的准备学生在生物科学的职业生涯。 学生将在当地（每月），区域和国际会议上展示他们的研究结果。 每年的C。优雅的会议促进了初级科学家的发展，因为许多发言者是从研究生提交的摘要中挑选出来的。 这项工作的结果也将包括在UB的本科信号转导课程的讲座中。 从该项目的遗传筛选中获得的突变体将存放在小杆线虫遗传中心，该中心将向任何要求它们的研究人员分发。 新的基因和表型描述也将被纳入Wormbase，一个在线开放获取资源。