The locomotory system of nematodes is the target of many currently used anthelminthics, since disruption of locomotory behavior interferes with the normal processes by which many nematodes maintain their position within the host. The problem of genetic drug resistance is making many of the available drugs less effective, so it is important to develop new generations of anti-nematdde drugs. The proposed research aims to describe new intercellular signaling systems that are important in the motornervous system that controls locomotion. Our strategy is based on our previous work in which we isolated and sequenced a large family of 29 novel endogenous neuropeptides in the parasitic nematode, Ascaris suum. Preliminary experiments have shown that almost all of the peptides tested have potent activity .on the neuromuscular system of Ascaris. Some cause paralysis, others exaggerate locomotory movements. Neuropeptides, therefore, play an important role in the overall activity of the motornervous system. There is every indication that there are many more peptides than the ones we have isolated so far. There is no indication that the currently available peptides are the most potent, so we propose to isolate new peptides, concentrating on those that are present in the motornervous system, in order to detect new peptides that have potent physiological activity. This is basic research upon which new generations of anthelminthics can ultimately be developed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI015429-28
Application #
7357486
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Rogers, Martin J
Project Start
2006-02-15
Project End
2011-01-31
Budget Start
2008-02-01
Budget End
2009-01-31
Support Year
28
Fiscal Year
2008
Total Cost
$340,540
Indirect Cost
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
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
Jarecki, Jessica L; Viola, India R; Andersen, Kari M et al. (2013) Three independent techniques localize expression of transcript afp-11 and its bioactive peptide products to the paired AVK neurons in Ascaris suum: in situ hybridization, immunocytochemistry, and single cell mass spectrometry. ACS Chem Neurosci 4:418-34
Reinitz, Catharine A; Pleva, Anthony E; Stretton, Antony O W (2011) Changes in cyclic nucleotides, locomotory behavior, and body length produced by novel endogenous neuropeptides in the parasitic nematode Ascaris suum. Mol Biochem Parasitol 180:27-34
Jarecki, Jessica L; Frey, Brian L; Smith, Lloyd M et al. (2011) Discovery of neuropeptides in the nematode Ascaris suum by database mining and tandem mass spectrometry. J Proteome Res 10:3098-106
Sithigorngul, Paisarn; Jarecki, Jessica L; Stretton, Antony O W (2011) A specific antibody to neuropeptide AF1 (KNEFIRFamide) recognizes a small subset of neurons in Ascaris suum: differences from Caenorhabditis elegans. J Comp Neurol 519:1546-61
Jarecki, Jessica L; Andersen, Kari; Konop, Christopher J et al. (2010) Mapping neuropeptide expression by mass spectrometry in single dissected identified neurons from the dorsal ganglion of the nematode Ascaris suum. ACS Chem Neurosci 1:505-519
Nanda, Jennifer Cho; Stretton, Antony O W (2010) In situ hybridization of neuropeptide-encoding transcripts afp-1, afp-3, and afp-4 in neurons of the nematode Ascaris suum. J Comp Neurol 518:896-910
Yew, Joanne Y; Davis, Ralph; Dikler, Sergei et al. (2007) Peptide products of the afp-6 gene of the nematode Ascaris suum have different biological actions. J Comp Neurol 502:872-82
McKenna, Philip M; Koser, Martin L; Carlson, Kevin R et al. (2007) Highly attenuated rabies virus-based vaccine vectors expressing simian-human immunodeficiency virus89.6P Env and simian immunodeficiency virusmac239 Gag are safe in rhesus macaques and protect from an AIDS-like disease. J Infect Dis 195:980-8

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