Developmental Specification of a Polymodal Nociceptor in C. elegans

所有的动物都依靠感知和对环境做出反应的能力来生存。对疼痛或有害刺激的感知起着重要的保护作用，并使动物退出或避免潜在的破坏性刺激。在我们对检测伤害性刺激(伤害性感受器)的神经细胞如何发展的理解上，仍有很大的差距。这个项目将使用小蛔虫，线虫，来发现有助于伤害性感受器发育的基因。这一发现将有利于研究从无脊椎动物到人类的各种有机体的研究人员。特别是，了解伤害性神经细胞的发育规范可能会提供新的方法来管理跨物种的厌恶和疼痛。研究生和本科生，包括女性和少数民族学生，将参加这些学习。布法罗大学(UB)是一个非常多样化的校园，为指导少数族裔学生提供了一个很好的机会。这笔助学金将为一名不提供本科生研究机会的文理学院本科生提供暑期津贴。提供早期接触假说驱动的研究对于学生为生物科学的职业生涯做准备是至关重要的。学生们将在当地、地区和国际会议上展示他们的研究成果。这项工作的发现将包括在亚利桑那州立大学本科生发育生物学课程的讲座中，并将成为研究生专题研究课程的基础。线虫的主要伤害性感受器是两个ASH头部感觉神经元。这些神经元检测多种形式的厌恶刺激。该项目旨在揭示ASHS在其自然环境中在活体动物中的神经元身份编码。拟议的实验将首先确定线虫配对的类同源域转录因子UNC-42在ASH伤害性神经元发育规范中的作用。然后，RNAi筛选将确定确定ASH身份所需的完整转录因子队列。这一奖项产生的转基因动物将被存放在线虫遗传中心，该中心将把它们分发给任何要求它们的研究人员。新的基因和表型描述也将被纳入在线开放获取资源“虫库”http://www.wormbase.org/中。

All animals rely on their ability to sense and respond to the environment to survive. The perception of pain or noxious stimuli serves an important protective function and causes animals to withdraw from or avoid potentially damaging stimuli. There are still large gaps in our understanding of how the nerve cells that detect noxious stimuli (nociceptors) develop. This project will use the small roundworm, C. elegans, to discover the genes that contribute to nociceptor development. The findings will benefit researchers working in organisms ranging from invertebrates to humans. In particular, understanding the developmental specification of nociceptive nerve cells may provide new ways to manage aversion and pain across species. Graduate 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 offer opportunities for 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 regional and international meetings. Findings from this work will be included in the lectures for UB's undergraduate Developmental Biology course and will form the basis for a special topics research course for graduate students. The primary nociceptors in C. elegans are the two ASH head sensory neurons. These neurons detect multiple forms of aversive stimuli. This project aims to reveal the neuronal identity code of the ASHs in their native environment in live animals. The proposed experiments will first define the role of the C. elegans paired-like homeodomain transcription factor UNC-42 in the developmental specification of the ASH nociceptive neurons. RNAi screening will then identify the complete cohort of transcription factors required to establish ASH identity. Transgenic animals resulting from this award 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" http://www.wormbase.org/ ,an online open access resource.