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.
| Zamanian, Mostafa; Agbedanu, Prince N; Wheeler, Nicolas J et al. (2012) Novel RNAi-mediated approach to G protein-coupled receptor deorphanization: proof of principle and characterization of a planarian 5-HT receptor. PLoS One 7:e40787 |
| Dalzell, Johnathan J; McVeigh, Paul; Warnock, Neil D et al. (2011) RNAi effector diversity in nematodes. PLoS Negl Trop Dis 5:e1176 |
| McVeigh, Paul; Mair, Gunnar R; Novozhilova, Ekaterina et al. (2011) Schistosome I/Lamides--a new family of bioactive helminth neuropeptides. Int J Parasitol 41:905-13 |
| Zamanian, Mostafa; Kimber, Michael J; McVeigh, Paul et al. (2011) The repertoire of G protein-coupled receptors in the human parasite Schistosoma mansoni and the model organism Schmidtea mediterranea. BMC Genomics 12:596 |
| Atkinson, Louise E; McVeigh, Paul; Kimber, Michael J et al. (2010) A PAL for Schistosoma mansoni PHM. Mol Biochem Parasitol 173:97-106 |
| Pierson, Lisa; Mousley, Angela; Devine, Lynda et al. (2010) RNA interference in a cestode reveals specific silencing of selected highly expressed gene transcripts. Int J Parasitol 40:605-15 |
| Novozhilova, Ekaterina; Kimber, Michael J; Qian, Hai et al. (2010) FMRFamide-like peptides (FLPs) enhance voltage-gated calcium currents to elicit muscle contraction in the human parasite Schistosoma mansoni. PLoS Negl Trop Dis 4:e790 |
| Mousley, Angela; Novozhilova, Ekaterina; Kimber, Michael J et al. (2010) Neuropeptide physiology in helminths. Adv Exp Med Biol 692:78-97 |
| Thornhill, J; Coelho, P M Z; McVeigh, P et al. (2009) Schistosoma mansoni cercariae experience influx of macromolecules during skin penetration. Parasitology 136:1257-67 |
| McVeigh, Paul; Mair, Gunnar R; Atkinson, Louise et al. (2009) Discovery of multiple neuropeptide families in the phylum Platyhelminthes. Int J Parasitol 39:1243-52 |
Showing the most recent 10 out of 21 publications
