Regulation of Chemoreceptor Gene Expression in C. elegans

动物必须改变它们的发育和行为以适应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介导的。然而，环境线索被翻译成基因表达的适当变化的机制尚不完全清楚。本研究的目的是研究秀丽隐杆线虫模式生物中化学感觉受体基因表达受环境信号调控的分子途径。秀丽隐杆线虫通过在少量化学感觉神经元中表达的化学感觉受体蛋白对环境中的化学物质作出反应。以前的研究表明，蠕虫在不同的环境条件下会改变它们的化学感觉行为，并且化学感觉受体基因的表达受到外部信号的调节。这些数据导致了一种假设，即环境介导的行为改变可能部分是通过化学感觉受体基因表达的变化来介导的。在之前的资助期内，由KIN-29激酶、MEF-2转录因子和HDA-4组蛋白去乙酰化酶蛋白组成的信号通路被证明以一种可能依赖于化学感觉神经元活动水平的方式调节化学感觉受体基因子集的表达，而化学感觉神经元活动水平反过来又可能受到外部信号的调节。本建议的具体目标是：目标1。探索神经元活动介导的kin29对化学感觉受体基因表达的调控。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。KIN-29的作用机制将通过生化方法进行研究。目标2。在kin -29调控的CR基因表达通路中作用的其他基因分析。这一目的的目标是利用秀丽隐杆线虫的遗传能力来识别kin -29调节途径的其他成分。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以类似的过程起作用，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，本科生人数众多。生物是最受欢迎的专业，该系致力于为所有感兴趣的本科生提供强大的科学训练，参与研究是其中的重要组成部分。在过去的资助期内，有3名本科生参与了该项目，并作为共同作者发表了论文。培养研究生和本科生的科学研究方法是本工作的目标。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。

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.