Project Leader:   
Don Moerman

Involved Institution:   
University of British Columbia  

Technology Applications:   
Target and drug discovery  

Research Funding Program:   
Competition III

The soil nematode C. elegans is an ideal model organism to study gene function because it has a small genome that has been fully sequenced and is a simple multicellular organism.  There are approximately 20,000 genes in the nematode and comparative sequence analysis of the human and C. elegans genomes reveals that these two widely divergent species have about 7,000 genes in common. By studying the human gene equivalent in nematodes, it will allow researchers to determine if they are pursuing an important research investigation.

The goal of this project is to create strains of the nematode by deleting, or knocking out, specific genes, providing a resource for the worldwide research community.

These strain variants help determine the function of the genes in various biological contexts. The researchers, in collaboration with international partners, have isolated 2000 strain variants and this project will provide another 4000 variant strains, targeting genes specific to nematodes in addition to the genes that are shared with humans. These common genes, when dysfunctional in humans, can lead to genetic disorders or susceptibility to cancers so understanding their basic biological functions could directly impact medical care. Nematodes are major agricultural pests and determining the function of nematode-specific genes may suggest targets for nematicide development.

However, only 15% of nematode genes have mutations indicative of their function. Therefore, this project will delete, or knock out, thousands more genes to determine their function. To create the strain variants, the researchers use a PCR-based technique related to transposable elements that substitutes a chemical mutagen for Tc1. The genes that are targeted for deletion are chosen after consultation with the research community and a scientific advisory board. The focus is on nematode genes with strong sequence similarity to human genes associated with human diseases, particularly if no function is yet known. The other focus is on genes unique to nematodes because this group of genes offer the best potential targets for nematicides to protect human health and agricultural crops.