Function of a Neuropeptide Gene Family in C. elegans

线虫神经肽基因家族的功能

• 批准号: 6472496
• 负责人: CHRISTINE LI
• 金额: $ 37.22万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-16 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6472496
• 关键词: Caenorhabditis elegans; functional /structural genomics; gene expression; gene mutation; gene targeting; genetic models; immunocytochemistry; informatics; neurogenetics; neuropeptide receptor; neuropeptides; protein localization; protein structure function; reporter genes

DESCRIPTION (provided by applicant): The role of neuropeptides in modulating complex behavior in the mammalian nervous system is slowly being elucidated. The recent identification of neuropeptides involved in circadian rhythms, sleep patterns, and obesity highlights the diversity of behaviors in which neuropeptides play a role. Because neuropeptides are often multifunctional and have overlapping functions with other peptides, their precise role in many behaviors have been difficult to assess. We are interested in examining the function, regulation, and signaling pathways of a neuropeptide gene family in a simple model system, the roundworm Caenorhabditis elegans. The simplicity of the C. elegans nervous system and the ability to manipulate the animal genetically allows use of approaches in C. elegans not readily available in other systems, such as mammals. Furthermore, because the genome of C. elegans has been completely determined, we are able for the first time to target specific neuropeptide gene families for study. By BLAST searches, there are at least 54 predicted neuropeptide genes encoding over 100 distinct neuropeptides in C. elegans. We have focused on examining the FMRFamide-related gene family, which represents the single largest neuropeptide gene family in any organism. About 50 percent of the nerve cells in C. elegans use FMRFamide-related peptides (FaRPs). Over 23 C. elegans genes encode FaRPs, and at least one of these genes does not have functional overlap with the other genes. We will study the function of this gene family by isolating deletion mutants for each gene. In addition, we will begin to match the FaRP ligand to specific receptors by using a combined bioinformatics and experimental approach. Animals in which the receptors are inactivated will be isolated and characterized. Insights into how neuropeptides function in C. elegans may give clues into how neuropeptides are used in higher animals, such as man. In addition, because C. elegans is the current genetic model system for parasitic nematodes, elucidating the functions of neuropeptides and their signaling pathways may identify new antihelmintic drug targets.

描述(申请人提供)：神经肽在调节中的作用 哺乳动物神经系统中的复杂行为正在慢慢地被阐明。 最近发现的与昼夜节律、睡眠有关的神经肽 模式，而肥胖突出了行为的多样性 神经肽起着一定的作用。因为神经肽通常是多功能的， 与其他多肽有重叠的功能，它们在许多 行为一直很难评估。我们有兴趣研究一下 一个神经肽基因家族的功能、调节和信号转导途径 简单的模型系统，线虫秀丽线虫。的简单性 线虫的神经系统和操纵动物的能力 基因上允许在线虫中使用在 其他系统，如哺乳动物。此外，因为线虫的基因组 已经完全确定了，我们第一次能够瞄准 用于研究的特定神经肽基因家族。通过爆炸搜索，有 至少54个预测的神经肽基因编码100多个不同的神经肽 在线虫中。我们重点研究了FMRFamide相关基因家族， 它代表了任何有机体中最大的单一神经肽基因家族。 线虫体内约50%的神经细胞使用FMRFamide相关基因 多肽(FARP)。超过23个线虫基因编码FARP，至少有一个 这些基因与其他基因在功能上没有重叠。我们会 通过分离每个基因的缺失突变体来研究该基因家族的功能 吉恩。此外，我们将开始将FARP配体与特定的受体进行匹配 通过使用生物信息学和实验相结合的方法。其中的动物 失活的受体将被分离和鉴定。洞察 线虫体内神经肽的功能可能为神经肽如何发挥作用提供线索 用于高等动物，如人类。此外，因为线虫是 当前寄生线虫遗传模型系统及其功能的阐明 神经肽及其信号通路的研究可能识别新的抗蠕虫药物 毒品目标。