Project Leader:   
David Baillie

Project Co-Investigator:   
Don Moerman

Involved Institution:   
Simon Fraser University, University of British Columbia, BC Cancer Agency

Technology Applications:   
Gene expression markers, Preclinical research tools, Fluorescence proteins

Research Funding Program:   
Competition II

Building upon the first Genome BC C. elegans research project, this study is helping researchers discover the function of 2,ooo genes identified in the nematode that are similar to genes in humans. This project plans to describe the gene expression and protein network profiles in C. elegans, the transparent worm used as a model organism to study gene function. By discovering the function of genes in the worm and where they impact cellular processes, this project will develop a better understanding of how the equivalent genes function in humans. Researchers will use a number of techniques, including serial analysis of gene expression, GFP constructs, and yeast 2-hybrid screens to determine the RNA and protein profiles in specific tissues of C. elegans. The GFP constructs show a gene’s expression pattern by making the target cell or organ fluoresce green. By the end of the project in March 2006 more than 2000 expressing GFP constructs will have been made, providing the largest GFP construct collection for C. elegans study worldwide.

To determine the expression pattern of genes, this project is producing functional Green Fluorescent Protein (GFP) fusion constructs. These GFP constructs make cells glow green when a gene is expressed, easy to observe in these transparent worms. The project will initially target the same set of genes as another Genome BC project, Comprehensive Study of Gene Knockouts in C. elegans. By discovering the function of genes in the worm (what the genes do) and their expression (where they do it), it will help understand how the equivalent genes function in humans. In the first 20 months of the project, this project made 900 GFP constructs with expression, the largest promoter::GFP strain collection available for C. elegans worldwide.

Recording GFP construct embryos during development will provide detailed expression patterns for genes activated during embryogenesis plus an understanding of how expression patterns change during development. The researchers will also use serial analysis of gene expression (SAGE) on specific cell types to establish a baseline of RNA expression and determine which genes are expressed in each cell type. Then yeast two-hybrid and one-hybrid screens will be used to identify interacting proteins, first concentrating on muscle tissue and constructing a protein interaction matrix.

All gene expression and protein interaction data will be deposited into public databases. The proposed profiles will give detailed information about the complexity of protein expression and intracellular protein interactions. This work will help researchers understand not only genetic defects involving the malfunction of a single gene, but the way in which genes and their products interact within developing cells, tissues, and organs.