“C. elegans, a soil nematode, was the first complex organism to be sequenced; the worm has muscles, it has intestines, it has a nervous system, and a little brain and can thus serve as a model organism,” says Dr. David Baillie of Simon Fraser University. “Humans and worms have a common ancestor about 500-700 million years ago. Our collaborators have used the results from the Human Genome Sequencing Project to identify genes (orthologous genes) that are similar in both humans and worms. Studying these genes in worms will help us understand their functions in humans. For example, studying the neurons of worm may help us learn how to treat human neurological diseases.”
The project “Expression Profiles of Cells and Tissues in C. elegans”, is a large-scale research project supported by Genome British Columbia, and by Genome Canada (50%), a not-for-profit corporation leading a national strategy on genomics and proteomics with $375 million in funding from the Government of Canada.
The research team chose to study over 5,000 orthologous genes, which were identified using an automated process developed by Dr. Sonnhammer in Sweden, where the ~30,000 human genes were compared with the ~20,000 worm genes.
Taking advantage of another genomics project, directed by one of the co-investigators, Dr. Moerman of the University of British Columbia, about 2,000 of the genes identified in Sweden, whose function is neither understood either or in worms or humans, were knocked out. By discovering the function of genes in the worm (what the genes do) and their expression (where the genes do it), the research team is confident it will be able to understand the equivalent genes function in humans, whether in muscles, the nervous system, or other areas.
According to Dr. Baillie, “we will do a chromogenic construct for each of the orthologues on the list which will cause the cells or tissue where a gene ‘turns on’ to fluoresce green (by using a coloured protein derived from a jellyfish). This will allow us to know when in development and in which cell types a given gene is expressed. Because the worm is transparent, it is easy to see the fluorescence of the gene in question.”
This work will in turn help understand not only genetic defects involving the malfunction of a single gene, but also the way in which genes and their products interact with developing cells, tissues and organs.
Dr. Baillie considers this research project important because it is way of understanding human genes via worm genes – only faster and at a lower cost. The human genome may have been sequenced, but many genes in humans still have an unknown function. “We want to know how humans work, on the basis of worms – a simple organism. My goal scientifically has always been to understand what genes do, and how the genome is structured and makes the organism. The question is whether the mechanism of worms is the same as in humans. We are attacking that on an international basis. Even to this day, there are people who say, ‘what is the use of all this information?’ To that we say, ‘we want to know how organisms work!”
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