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Sometimes a great discovery begins by being in the right place at
the right time. That's what happened in 1996, when Drs. Alex MacKenzie
and Philippe Gros began sharing ideas at a scientific meeting of the
Canadian Genetic Disease Network (CGDN) in Vancouver. They have since
made a groundbreaking discovery in the battle against Legionnaire's
Disease.
It was almost by chance that Drs. MacKenzie and Gros discovered that
their different fields of study weren't so different after all. Dr. MacKenzie,
a CGDN investigator at the Children's Hospital of Eastern Ontario, had
identified a gene called Naip while screening for the gene that causes
Spinal Muscular Atrophy, a fatal neurological disease in children. Dr.
Gros, a professor in the Department of Biochemistry at McGill University,
had been working on genetic susceptibility to Legionnaire's disease in
the mouse. Their chance meeting in Vancouver sowed the seeds of what would
become an important new discovery - that Naip5 plays a role in fighting
Legionnaire's Disease.
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Gene discovery offers hope
CGDN researchers used a technique called "functional complementation" to identify Naip5, a gene associated with Legionnaire's Disease. Pieces of mouse chromosome 13 were inserted into mice that were susceptible to Legionella infection. When a piece of DNA containing the Naip5 gene was inserted into these same mice, they became resistant to infection.
"This shows that Legionella replication in mice is regulated by a host gene, and highlights the role of the host's genetic makeup in the infectious process," explains Dr. Silvia Vidal, a researcher at the University of Ottawa. "In the last few years, several host genes that provide protection against both viral and bacterial pathogens have been identified. We expect this process will accelerate with the development of better genomic technologies and the availability of the human and mouse genome sequences."
Legionnaire's Disease is a severe form of pneumonia that first appeared during a 1976 Legionnaire's Convention in Philadelphia, Pennsylvania. Approximately 10-15 per cent of these infections are fatal. It is typically transmitted to humans through aerosols produced by air conditioning cooling units, showers and faucets.
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A new research collaboration soon followed, involving Drs. MacKenzie, Gros and Silvia Vidal, a scientist at the University of Ottawa. Together, they determined that when a piece of DNA containing the Naip5 gene was inserted into mice, the mice became resistant to Legionella infection. Their results were published in the January 2003 issue of Nature Genetics.
"We have essentially discovered that a protein involved in the survival of neurons is also involved in the ability of macrophages (a part of the immune system that attacks bacteria) to control infection with Legionella," explains Dr. Gros. "With this new information, we hope to determine whether human Naip-related genes play a role in the pathogenesis of Legionnaire's Disease in people."
He adds that the Vancouver meeting presented an opportunity for him and Dr. MacKenzie to merge their two fields of study. "It's the ideal story of scientists being brought together, coming from different angles," says Dr. Gros, who is also a scientist at the McGill University Cancer Centre, and the McGill Center for Host Resistance. "This definitely would not have come together without CGDN."
Dr. Michael Hayden, CGDN Scientific Director and Director of the Centre for Molecular Medicine and Therapeutics in Vancouver, says one of the CGDN's strengths is the informal collaborations it facilitates between scientists from across the country. "One of the goals at CGDN is to foster collaboration among people, and this is an example of what can happen as a result of these chance meetings for informal interaction," says Dr. Hayden, adding that CGDN-supported research has now led to the discovery of more than 50 genes linked to disease.
Not only was CGDN's annual scientific meeting the launching pad for this discovery, which Gros calls a critical step to novel therapeutics in the future, but the network also funded the project from day one. It contributed approximately $75,000 (a partial figure) over the past 10 years, and supplied core facilities. The research project also received grants from the Canadian Institutes of Health Research and Innovation Quebec.
Looking ahead, the scientists say they need to better understand their discovery, including research into whether human Naip-related genes play a role in the pathogenesis of Legionnaire's Disease in humans. "We're still in the beginning stages, but it's an exciting process," adds Dr. Vidal.
www.cgdn.ca
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