STRUCTURE AND FUNCTION OF SCHISTOSOME NEUROPEPTIDE F

描述(改编自申请者摘要)：血吸虫是寄生虫 扁虫在世界各地造成了无法估量的痛苦 世界。新型抗血吸虫药物的开发因缺乏药物而受阻 血吸虫生物学的关键方面的知识，包括神经系统。 血吸虫神经系统的神经肽成分提供了重要的 有可能成为开发选择性化疗药物的靶点。这个 扁虫体内含量最丰富的神经肽是神经肽F(NPF)，它是 脊椎动物神经肽Y(NPY)家族的多肽。这一家族的多肽 具有关键的结构特征，从扁虫到人类都是如此， 这种守恒很可能是一种关键的生理学 角色。然而，NPY多肽的功能通常知之甚少。 本提案旨在描述NPY/NPF信令的主要组成部分 系统在血吸虫和建立基线功能数据上的作用 蠕虫中的NPF。这些数据将使用一系列分子， 生物化学和生理学方法，目的是在结构上表征 内源性血吸虫神经肽和神经肽受体，鉴定 编码它们的基因，研究它们的生化和生理学 相关的细胞内信号系统及其作为药物的潜力 目标。此外，对这种多肽在扁虫中的作用的评估是 可能确定关键的基本功能，这些功能解释了非凡的 NPY家族多肽中的结构保守性。

DESCRIPTION (Adapted from the Applicant's Abstract): Schistosomes are parasitic flatworms that inflict an immeasurable amount of suffering throughout the world. The development of novel anti-Schistosoma is hindered by our lack of knowledge of key aspects of schistosome biology, including the nervous system. The neuropeptide component of the schistosome nervous system offers significant potential as a target for development of selective chemotherapeutic agents. The most abundant neuropeptide in flatworms is neuropeptide F (NPF), a member of the vertebrate neuropeptide Y (NPY) family of peptides. This family of peptides have key structural attributes which are conserved from flatworms to humans, and this conservation is likely to be a consequence of a pivotal physiological role. However, the functions of NPY peptides is generally poorly understood. This proposal aims to characterize the main components of the NPY/NPF signaling system in schistosomes and to establish baseline functional data on the role of NPF in the worm. These data will be generated using a range of molecular, biochemical and physiological approaches which aim to structurally characterize the endogenous schistosome neuropeptide and neuropeptide receptor, identify the genes encoding them, investigate the biochemistry and physiology of the associated intracellular signaling system and evaluate its potential as a drug target. Furthermore, evaluation of the role of this peptide in flatworms is likely to identify key basic functions, which account for the remarkable structural conservation seen in NPY family peptides.