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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI103790-01
Application #
8430302
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Mcgugan, Glen C
Project Start
2013-06-01
Project End
2015-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$169,242
Indirect Cost
$51,742
Name
University of Wisconsin Madison
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715