Regulation of Chemoreceptor Gene Expression in C. elegans

秀丽隐杆线虫化学感受器基因表达的调控

• 批准号: 0542372
• 负责人: Piali Sengupta
• 金额: $ 36万
• 依托单位: Brandeis University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0542372&HistoricalAwards=false
• 关键词: Regulation; Chemoreceptor; Gene; Expression; C.

Animals must alter their development and behavior in response to ever-changing environmental conditions. These adaptive changes are ultimately mediated via changes in gene expression patterns. However, the mechanisms by which environmental cues are translated into the appropriate changes in gene expression are not fully understood. The goal of this proposal is to investigate the molecular pathways by which the expression of chemosensory receptor genes is regulated by environmental signals in the model organism C. elegans. C. elegans responds to chemicals in its environment via chemosensory receptor proteins expressed in a small number of chemosensory neurons. It has previously been shown that worms alter their chemosensory behaviors under different environmental conditions, and that the expression of chemosensory receptor genes is modulated by external cues. These data have led to the hypothesis that environment-mediated behavioral changes may in part, be mediated via changes in chemosensory receptor gene expression. In the previous funding period, a signaling pathway comprised of the KIN-29 kinase, the MEF-2 transcription factor, and the HDA-4 histone deacetylase proteins were shown to regulate the expression of a subset of chemosensory receptor genes in a manner that may be dependent on levels of chemosensory neuron activity, which in turn may be regulated by external signals. The specific aims of this proposal are to: AIM 1. Explore neuronal activity-mediated regulation of chemosensory receptor gene expression by KIN-29. The goal of this aim is to explore how electrical activity of the neuron plays a role in regulating KIN-29-mediated gene expression. The mechanisms of KIN-29 function will be investigated using biochemical methods. AIM 2. Analysis of additional genes acting in the KIN-29-regulated pathway for CR gene expression. The goal of this aim is to exploit the genetic power of C. elegans to identify additional components of the KIN-29-regulated pathway. Since molecules related to KIN-29, MEF-2 and HDA-4 have been shown to act in similar processes in vertebrates, it is expected that principles derived from the proposed experiments will be generally applicable in other systems. Brandeis University is a private liberal arts University with a large undergraduate population. Biology is the most popular major, and the Department is committed to providing all interested undergraduates with strong scientific training of which participation in research is a vital component. Three undergraduates were involved with this project in the past funding period and were included as co-authors on publications. It is a goal of this work to train graduate and undergraduate students in the scientific research method. Training and knowledge provided by this work will enable them to be effective in their future careers of choice, and to effectively communicate scientific information to the public.

动物必须改变其发育和行为以应对不断变化的环境条件。这些适应性变化最终是通过基因表达模式的变化来介导的。然而，环境因素转化为基因表达适当变化的机制尚不完全清楚。该提案的目的是研究模型生物线虫中化学感应受体基因的表达受环境信号调节的分子途径。 线虫通过少数化学感应神经元表达的化学感应受体蛋白对其环境中的化学物质做出反应。此前已有研究表明，线虫在不同的环境条件下会改变其化学感应行为，并且化学感应受体基因的表达受到外部线索的调节。这些数据导致了这样的假设：环境介导的行为变化可能部分是通过化学感应受体基因表达的变化来介导的。在之前的资助期间，由 KIN-29 激酶、MEF-2 转录因子和 HDA-4 组蛋白脱乙酰酶蛋白组成的信号通路被证明可以以可能依赖于化学感应神经元活性水平的方式调节化学感应受体基因子集的表达，而化学感应神经元活性水平反过来又可能受到外部信号的调节。本提案的具体目标是： 目的 1. 探索 KIN-29 神经元活动介导的化学感应受体基因表达调节。该目的的目的是探索神经元的电活动如何在调节 KIN-29 介导的基因表达中发挥作用。将使用生化方法研究 KIN-29 功能的机制。 目的 2. 分析作用于 KIN-29 调节 CR 基因表达途径的其他基因。该目标的目的是利用线虫的遗传能力来识别 KIN-29 调控途径的其他成分。 由于与 KIN-29、MEF-2 和 HDA-4 相关的分子已被证明在脊椎动物中具有类似的过程，因此预计从所提出的实验中得出的原理将普遍适用于其他系统。布兰迪斯大学是一所私立文理大学，拥有大量本科生。生物学是最受欢迎的专业，该系致力于为所有感兴趣的本科生提供强有力的科学培训，其中参与研究是一个重要组成部分。三名本科生在过去的资助期间参与了该项目，并作为共同作者发表了出版物。这项工作的目标是培养研究生和本科生的科学研究方法。这项工作提供的培训和知识将使他们能够在未来选择的职业中发挥作用，并有效地向公众传播科学信息。