Our research is focused on:
1. Generation and public dissemination of high-quality parasitic-nematode genomic data;
2. Creation and implementation of bioinformatics approaches, that can be applied uniformly across the multiple growing nematode datasets, to characterize and understanding these sequences;
Functional Classifications:
Gene Ontology
KEGG
3. Applying functional genomics tools across the phylum. Beyond the acquisition of sequence data, to understand the biology of nematodes requires determination of the function of gene products on distantly related nematode species on a genome-wide scale;
Functional Genomics:
Microarray studies
Proteomics
4. Exploring the genome data to provide an entry point toward a deep understanding of the phylum Nematoda at the molecular level;
Main projects:
1. Identification and characterization of novel nematode-specific protein families
Abstract
Nematodes diverged evolutionarily from other animals between 600-1200 MYA, adapting a number of phyla-specific features along the way. Proteins with specificity to nematodes may serve as excellent targets for drugs with low toxicity to humans and other vertebrates or for environmentally safe pesticides. Guided by the importance of identifying nematode-specific proteins and aided by the increase of nematode sequences in the public databases, we have created computational based methods that can detect highly conserved regions in a robust fashion. Our approach identified putative coding sequences conserved across the phylum Nematoda or nematode subgroups. We are doing extensive functional and structural characterization of all identified nematode-specific protein families, and several will be characterized in more detail with an emphasis on postulating molecular or cellular function.
2. Evolution of the nematode intestine
Abstract
The nematode intestine is a major organ responsible for nutrient digestion and absorption; it is also involved in many other processes such as reproduction, immunity, stress response, and aging. Recently, the intestine has become an effective control target against parasitic nematodes. However, the lack of gene and gene expression information of the intestine has impeded breakthroughs. We sampled various transcribed genomes from intestine of several parasitic nematode species and made the largest collections of intestine-expressed genes for any parasitic nematodes. Cross-species comparison to the intestine of free-living adult C. elegans is underway to investigate conservation of intestinal gene expression at the tissue level across the nematodes. Our study aims to provide novel insights into the nematode intestine and laid foundations for further comparative studies on biology, parasitism, and evolution within the phylum Nematoda.
3. Nematode.net: additions and improvements of data navigation and comparative genomics of nematodes
Abstract
The web-accessible resource Nematode.net (www.nematode.net) provides access to genome data specific to free-living and parasitic nematodes. Nearly 300,000 Expressed Sequence Tags and 600,000 Genome Survey Sequences have been generated from 30 nematode species. Nematode.net provides NemaGene EST cluster consensus sequences, NemPep predicted translations and codon usage tables. The cluster pages have a 'cluster hub' which links to a G-browse view of the related EST cluster. The database also provides functional classification: i) a tree-viewer along with a web-based graphical display using the KEGG enzymatic pathway maps; ii) Gene Ontology associations displayed using the Amigo Browser.
Efforts were made to integrate it with other nematode-related specialized sites. Nematode.net users are able to link-out to all related C. elegans gene pages from each of NemaGene contig pages and Wormbase users can easily link to the proper contig pages within Nematode.net using a redirection enabled by a CGI scripts. The long-term goal of Nematode.net is to provide a useful, consistent, centralized and lasting database to the worldwide parasitology community.
4. A Genomic Approach to Parasites From the Phylum Nematoda
Abstract
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 both basic research as well as the development of effective diagnostics, vaccines, and new drugs. After completing the C. elegans genome, Washington University's Genome Sequencing Center (GSC) has generated and immediately made public over 210,000 expressed sequence tags (ESTs) from 25 nematode species, including representatives of all the major groups of human parasites such as hookworms, filarial worms, whipworms, and Ascarids. This proposal seeks to extend the available parasitic nematode sequence data and enhance its value to the research community through three aims. First, we will generate 125,000 new sequences from parasitic nematodes for less than half the cost per read of our original 1999 proposal. Sequencing efforts will focus on normalized libraries from the prevalent human and animal geohelminths Ascaris and hookworm that together infect over 2 billion people with the goal of identifying over half of the genes in each species. An Ascaris microarray will be produced and used to examine differences in gene expression over embryogenesis and in adult organs. Second, we will use nematode.net and wormbase.org to provide the parasitology community with bioinformatics databases and tools that are user-friendly, integrated, and lasting. Features to be created or expanded include the NemaGene cluster consensus sequences assembled from all available nematode sequence data, the NemPep database of nematode peptide sequences, Gene Ontology and Interpro protein domain classifications, and codon usage tables. In addition to its use by parasitologists, the availability of such information will provide important evolutionary context to developmental and genetic studies in the model C. elegans. Third, we will investigate novel areas of nematode biology by identifying nematode-specific protein domains with currently unknown functions. Regions of NemaGene sequences lacking Interpro domain coverage will be clustered and aligned by amino acid sequence to create new candidate domains with the goal of generating 250 novel high quality domain models for submission to Pfam/Interpro. Working with collaborators, a limited number of novel domains will be characterized in more detail with an emphasis on postulating molecular or cellular function.
For more details on our research please visit NEMATODE.NET and our list of PUBLICATIONS.
