STRUCTURE AND FUNCTION OF SCHISTOSOME NEUROPEPTIDE F

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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.