STRUCTURE AND FUNCTION OF SCHISTOSOME NEUROPEPTIDE F

描述（改编自申请人的摘要）：血吸虫是寄生虫 扁形虫，造成了无法估量的痛苦，整个 世界新型抗血吸虫病药物的开发受到我们缺乏 了解生物学的关键方面，包括神经系统。 溶酶体神经系统的神经肽成分提供了重要的 作为选择性化学治疗剂开发的靶点的潜力。的 扁形虫中最丰富的神经肽是神经肽F（NPF）， 脊椎动物神经肽Y（NPY）家族的肽。这个肽家族 具有从扁形虫到人类都保留的关键结构属性， 这种保守性很可能是一种关键的生理机制的结果， 作用然而，NPY肽的功能通常知之甚少。 该建议旨在表征NPY/NPF信号传导的主要成分 系统的作用，并建立基线功能数据 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，其目的是从结构上表征 内源性溶酶体神经肽和神经肽受体，鉴定 编码它们的基因，研究它们的生物化学和生理学。 相关的细胞内信号系统，并评估其作为药物的潜力 目标此外，评价这种肽在扁形虫中的作用是 可能会确定关键的基本功能，这些功能解释了 在NPY家族肽中观察到结构保守性。

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.