The research described in this proposal aims at determining the biological role of a family of 8 related endogenous neuropeptides, encoded by 4 different genes in A. suum. The peptide encoded by one gene has been shown to have very potent inhibitory activity on Ascaris suum muscle. We propose to characterize the biological activity of the remaining 7 peptides. We will also identify the cells (identified neurons, or non-neural cells) which make each peptide, and the site of the receptors for each peptide. We will also study the mechanism of action of each peptide by electrophysiological methods. There are preliminary indications that at least one of these peptides may be expressed in the intestine. We will thoroughly explore this hypothesis, since it suggests a potential new target for anti-nematode drugs, and, even more interesting, a different route for administration of drugs that would not necessitate penetration into the interior tissue space of the nematode.
The parasitic nematode Ascaris suum is a close relative of the human parasite Ascaris lumbricoides, which infects ca. 800 million people worldwide, causing childhood mortality and diminished adult health and productivity. The research described in this proposal aims at determining the biological role of a family of 8 related endogenous neuropeptides, encoded by 4 different genes in A. suum. The peptide encoded by one gene has been shown to have very potent inhibitory activity on Ascaris suum muscle. We propose to characterize the biological activity of the remaining 7 peptides. We will also identify the cells (identified neurons, or non- neural cells) that make each peptide, and the site of the receptors for each peptide. We will also study the mechanism of action of each peptide by electrophysiological methods. There are preliminary indications that at least one of these peptides may be expressed in the intestine. We will thoroughly explore this hypothesis, since it suggests a potential new target for anti-nematode drugs, and, even more interesting, a different route for administration of drugs that would not necessitate penetration into the interior tissue space of the nematode.
Konop, Christopher J; Knickelbine, Jennifer J; Sygulla, Molly S et al. (2015) Mass Spectrometry of Single GABAergic Somatic Motorneurons Identifies a Novel Inhibitory Peptide, As-NLP-22, in the Nematode Ascaris suum. J Am Soc Mass Spectrom 26:2009-23 |
Konop, Christopher J; Knickelbine, Jennifer J; Sygulla, Molly S et al. (2015) Different neuropeptides are expressed in different functional subsets of cholinergic excitatory motorneurons in the nematode Ascaris suum. ACS Chem Neurosci 6:855-70 |