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This is a story about a worm. But it isn’t the garden-variety invertebrate; this worm is microscopic, transparent and, according to researcher Marie Killeen, may provide the key to one day regenerating injured human spinal cords.

Dr. Killeen, an Assistant Professor in the Department of Chemistry and Biology, is studying a worm called Caenohabditis elegans or C. elegans. The first higher organism to have its genome sequenced, C. elegans serves as an animal model for human genetics research. In fact, the worm played a major role in three discoveries that jointly won the Nobel Prize in Physiology/Medicine in 2002 and in another breakthrough that won the same award in 2006.

Understanding Dr. Killeen’s research requires a brief lesson in anatomy and physiology: neurons are cells that move electrical impulses from one area of the body to another. In order to communicate with other cells, two types of projections extend from a neuron’s cell body: dendrites, which receive information, and axons, which send it out. The latter fibre is the basis of Dr Killeen’s research.

“I want to find out how axons know where to go during development,” she says.  Specifically, Dr. Killeen is interested in motor neurons, which transmit energy to muscles or glands. In C. elegans, motor neurons start on the ventral side (“belly”) of the worm and eventually extend to the dorsal cord (“back”). In mutated worms though, the neurons stop short at approximately the two-thirds mark. Dr. Killeen is investigating what genetic mutations cause this defect and what genes can correct or, alternatively, enhance the defect.

To begin unravelling the mystery, the worms are injected with DNA from the gene that produces green fluorescent protein (taken originally from the jellyfish Aequoria victoria). Since C. elegans is see-through, the fluorescence enables Dr. Killeen and her graduate students and research assistants to watch developing neurons under a microscope. This process enables the researchers to detect mutant strains of worms in which the axons have failed to migrate correctly. These mutants are presumed to have alterations in the genes that affect axon migration.

The process of identifying a gene is much like mailing a letter. You start with the genome (the city). You then identify the individual chromosome upon which the gene sits (the street). From there, you decipher exactly where the gene is located on the chromosome (the specific block). Next, you try to identify the precise “house” by injecting DNA to fix the defect in the strain of C. elegans containing the mutated gene.

“We are at the stage now where we know that one of eight genes is likely to be mutated in our strain” says Dr. Killeen. “We will now inject smaller pieces of DNA in the region to see if any of them correct the defects of the mutant strain. If one does, that will tell us, ‘Bingo, we’re there.’”

Unfortunately, as Dr. Killeen knows, discoveries in the genetics domain follow their own schedule. Before joining Ryerson several years ago, she worked as a post-doctoral student in the C. elegans research lab of Joe Culotti at Mount Sinai Hospital. Today, she maintains strong ties with her former colleagues. “The good side in this particular field of biology is that the work is collaborative. The bad side is that the work can be slow.”

On that note, with one of her current projects having reached its fifth anniversary, Dr. Killeen believes an end may be in sight and has begun writing a research paper. When the finish line wasn’t on the horizon, however, how did she stay motivated?

“I’m particularly interested in spinal cord regeneration in humans,” she says. “While my research isn’t directly aimed at that area, I hope any data we acquire on how normal nervous systems develop could assist with the reversal of spinal cord injuries, possibly due to the ability to force full or partial recapitulation of normal development after injury.”

Dr. Killeen’s research is supported by Ryerson University. She has also received past support from the Natural Sciences and Engineering Research Council of Canada.

Dana Yates is a Toronto-based freelance writer – www.danayates.ca

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