Parasitic nematodes infect over half the world's population, resulting in significant morbidity and mortality. Characterization of nematode genomes provides fundamental molecular information about these parasites accelerating basic research and development of new diagnostics and therapeutics. Washington University's Genome Center has generated and made public over 400,000 cDNAs from 30 parasitic species, sequenced 4 genomes to draft coverage with ten more underway including representatives of the major human parasitic groups. The three aims in this proposal analyze the expanding nematode sequences to substantially improve understanding of parasitic nematode biology and cellular pathways. First, we will develop and use bioinformatic tools to process, assemble, and annotate incoming data from all sequencing platforms. These genomic resources will also be disseminated to the wider research community through the centralized parasitic nematode database, Nematode.net. Second, analysis will focus on biochemical pathways conserved and/or taxonomically restricted including proteins that may prove useful as drug targets. Third, we will study the nature and implications of nematode-specific insertions and deletions in proteins involved in environmental information processing and endocrine system. The expected outcome will facilitate and promote the discovery and development of novel interventions to control these important parasites and reduced their associated morbidity and mortality.

Public Health Relevance

The continued development of molecular information, bioinformatics tools, and reagents for the study of parasitic nematodes is crucial, as they infect over half of the world's population and are a leading cause of human morbidity. The main goal of this project is to implement comparative genomics approaches to study the biology and cellular pathways of these important parasites, which on a long run will contribute to improved diagnostics, vaccines, and anthelmintic drugs for broad parasite control.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI081803-03
Application #
8076271
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Joy, Deirdre A
Project Start
2009-07-23
Project End
2014-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
3
Fiscal Year
2011
Total Cost
$308,241
Indirect Cost
Name
Washington University
Department
Genetics
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Leroux, Louis-Philippe; Nasr, Mohamad; Valanparambil, Rajesh et al. (2018) Analysis of the Trichuris suis excretory/secretory proteins as a function of life cycle stage and their immunomodulatory properties. Sci Rep 8:15921
Tyagi, Rahul; Maddirala, Amarendar Reddy; Elfawal, Mostafa et al. (2018) Small Molecule Inhibitors of Metabolic Enzymes Repurposed as a New Class of Anthelmintics. ACS Infect Dis 4:1130-1145
Zarlenga, D S; Mitreva, M; Thompson, P et al. (2018) A tale of three kingdoms: members of the Phylum Nematoda independently acquired the detoxifying enzyme cyanase through horizontal gene transfer from plants and bacteria. Parasitology :1-8
Martin, Ivonne; Djuardi, Yenny; Sartono, Erliyani et al. (2018) Dynamic changes in human-gut microbiome in relation to a placebo-controlled anthelminthic trial in Indonesia. PLoS Negl Trop Dis 12:e0006620
Magrini, Vincent; Gao, Xin; Rosa, Bruce A et al. (2018) Improving eukaryotic genome annotation using single molecule mRNA sequencing. BMC Genomics 19:172
Martin, John; Tyagi, Rahul; Rosa, Bruce A et al. (2018) A Multi-Omics Database for Parasitic Nematodes and Trematodes. Methods Mol Biol 1757:371-397
Rosa, Bruce A; McNulty, Samantha N; Mitreva, Makedonka et al. (2017) Direct experimental manipulation of intestinal cells in Ascaris suum, with minor influences on the global transcriptome. Int J Parasitol 47:271-279
Choi, Young-Jun; Bisset, Stewart A; Doyle, Stephen R et al. (2017) Genomic introgression mapping of field-derived multiple-anthelmintic resistance in Teladorsagia circumcincta. PLoS Genet 13:e1006857
Norice-Tra, Carmelle T; Ribeiro, José; Bennuru, Sasisekhar et al. (2017) Insights Into Onchocerca volvulus Population Biology Through Multilocus Immunophenotyping. J Infect Dis 216:736-743
McNulty, Samantha N; Tort, Jose F; Rinaldi, Gabriel et al. (2017) Genomes of Fasciola hepatica from the Americas Reveal Colonization with Neorickettsia Endobacteria Related to the Agents of Potomac Horse and Human Sennetsu Fevers. PLoS Genet 13:e1006537

Showing the most recent 10 out of 51 publications