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 #
5R01AI081803-04
Application #
8287160
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
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$308,241
Indirect Cost
$63,216
Name
Washington University
Department
Genetics
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Wang, Qi; Heizer, Esley; Rosa, Bruce A et al. (2016) Characterization of parasite-specific indels and their proposed relevance for selective anthelminthic drug targeting. Infect Genet Evol 39:201-11
McNulty, Samantha N; Strübe, Christina; Rosa, Bruce A et al. (2016) Dictyocaulus viviparus genome, variome and transcriptome elucidate lungworm biology and support future intervention. Sci Rep 6:20316
Zarlenga, Dante; Wang, Zhengyuan; Mitreva, Makedonka (2016) Trichinella spiralis: Adaptation and parasitism. Vet Parasitol 231:8-21
Wang, Qi; Rosa, Bruce A; Nare, Bakela et al. (2015) Targeting Lysine Deacetylases (KDACs) in Parasites. PLoS Negl Trop Dis 9:e0004026
Martin, John; Rosa, Bruce A; Ozersky, Philip et al. (2015) Helminth.net: expansions to Nematode.net and an introduction to Trematode.net. Nucleic Acids Res 43:D698-706
Tyagi, Rahul; Joachim, Anja; Ruttkowski, Bärbel et al. (2015) Cracking the nodule worm code advances knowledge of parasite biology and biotechnology to tackle major diseases of livestock. Biotechnol Adv 33:980-91
Tyagi, Rahul; Rosa, Bruce A; Lewis, Warren G et al. (2015) Pan-phylum Comparison of Nematode Metabolic Potential. PLoS Negl Trop Dis 9:e0003788
Cantacessi, Cinzia; Giacomin, Paul; Croese, John et al. (2014) Impact of experimental hookworm infection on the human gut microbiota. J Infect Dis 210:1431-4
Tang, Yat T; Gao, Xin; Rosa, Bruce A et al. (2014) Genome of the human hookworm Necator americanus. Nat Genet 46:261-9
Rutter, William B; Hewezi, Tarek; Abubucker, Sahar et al. (2014) Mining novel effector proteins from the esophageal gland cells of Meloidogyne incognita. Mol Plant Microbe Interact 27:965-74

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