Developmental Specification of a Polymodal Nociceptor in C. elegans

所有的动物都依靠它们对环境的感知和反应能力来生存。对疼痛或有害刺激的感知具有重要的保护功能，并使动物从潜在的破坏性刺激中退出或避免。我们对检测有害刺激的神经细胞（伤害感受器）是如何发育的理解仍有很大的差距。这个项目将使用小蛔虫，秀丽隐杆线虫，来发现有助于伤害感受器发育的基因。这一发现将使研究从无脊椎动物到人类等生物的研究人员受益。特别是，理解伤害性神经细胞的发育特征可能为跨物种管理厌恶和疼痛提供新的方法。研究生和本科生，包括女性和少数民族学生，将参与这些研究。布法罗大学（UB）是一个非常多元化的校园，为指导少数民族学生提供了很好的机会。这笔资金将用于支持文理学院本科生的暑期津贴，文理学院不提供本科生研究机会。让学生尽早接触到假设驱动的研究，对于让他们为从事生物科学的职业做好准备至关重要。学生们将在当地、区域和国际会议上展示他们的研究成果。这项工作的结果将被纳入UB本科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。秀丽隐杆线虫的主要伤害感受器是两个ASH头部感觉神经元。这些神经元检测多种形式的厌恶刺激。本项目旨在揭示活体动物中ASHs在其原生环境中的神经元身份编码。本实验将首先确定秀丽隐杆线虫配对同源结构域转录因子UNC-42在ASH伤害性神经元发育规范中的作用。然后，RNAi筛选将确定建立ASH身份所需的完整转录因子队列。该奖项产生的转基因动物将存放在隐杆线虫遗传中心，该中心将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资源“Wormbase”http://www.wormbase.org/。

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.