Function of a Neuropeptide Gene Family in C. elegans

描述（由申请人提供）：神经肽在调节 哺乳动物神经系统的复杂行为正在慢慢被阐明。 最近发现的神经肽参与昼夜节律，睡眠 肥胖突出了行为的多样性， 神经肽发挥作用。因为神经肽通常是多功能的， 与其他肽有重叠的功能，它们在许多 行为很难评估。我们有兴趣研究 神经肽基因家族的功能、调节和信号通路， 简单的模型系统，线虫秀丽隐杆线虫。的简单性 梭神经系统和操纵动物的能力 在遗传上允许使用C中的方法。优雅的不容易获得， 其他系统，如哺乳动物。此外，由于C. elegans 已经完全确定，我们能够第一次瞄准 研究特定神经肽基因家族。通过BLAST搜索， 至少54个预测的神经肽基因编码超过100种不同的神经肽 in C.优雅我们集中研究了FMRFamide相关基因家族， 它代表了任何生物体中最大的神经肽基因家族。 C.线虫使用FMRFamide相关 肽（FaRPs）。超过23摄氏度。线虫基因编码FaRPs，并且至少一种 这些基因与其它基因没有功能重叠。我们将 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。 基因此外，我们将开始将FaRP配体与特定受体相匹配 by using运用a combined结合bioinformatics生物信息学and experimental实验approach方法.动物在其中， 将分离和表征失活的受体。洞察 神经肽在C.秀丽线虫可能会提供线索， C. elegans是 寄生线虫的当前遗传模型系统，阐明其功能 神经肽及其信号通路可能识别新的抗蠕虫药 药物靶点

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.