Your Faculty / Fall 2005 - Faculty of Medicine - University of Calgary

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Research Your Faculty / Fall 2005
Mouse Prion Initiative
Investigating genetic mutations
and protein misfolding
By Natalie St-Denis
Dr. Frank Jirik
A
ll mammals carry the prion gene – a gene that scientists have linked
to the development of bovine spongiform encephalopathy (BSE)
in cows. And although extremely rare, extensive media coverage has
brought mad cow disease into our everyday vernacular. The prion
gene also has links to chronic wasting disease (CWD) in deer and to
a degenerative brain disease that spontaneously develops in humans,
known as Creutzfeldt-Jakob disease (CJD).
So how does a healthy prion protein misfold into a shape that
triggers a deadly disease – transforming a healthy, vibrant brain into
a spongy mass? That’s a question Dr. Frank Jirik, from the Department
of Biochemistry and Molecular Biology in the Faculty of Medicine
and lead investigator of the Mouse Prion Initiative at U of C, intends
to tackle. “We want to identify genes and proteins that are linked to
prion protein dysfunction and the subsequent degeneration of brain
cells,” says Jirik.
Jirik and his collaborators at the Universities of Calgary, Alberta
and British Columbia think healthy prion proteins in the brain may,
paradoxically, have a protective quality. “Our intentions are to explore
the kinds of environmental factors within the brain that allow prion
proteins to protect neurons. This may lead us to understand the ways
in which the misfolded-infective-form of the prion protein damage
brain cells,” says Jirik.
Currently, little is known about how prion diseases emerge and
how they are transmitted from one animal to another. Nor do scientists
understand why some exposed animals become infected while
others don’t. “Since only a small number of animals or humans exposed
to infective prions ever come down with the disease, it appears that
genetics play a determining factor on who develops the disease and
how fast the degeneration occurs,” explains Jirik.
The quest to uncover the mysteries behind prion diseases will
take place in controlled and ethically approved laboratory settings
using genetically engineered mice. Jirik and his collaborators will be
working with mice missing the prion gene to determine whether brain
cells undergo spontaneous damage in animals that also lack specific
antioxidant and anti-stress-response-system genes. Dr. Hans Vogel,
another key member of the research team, will also investigate prion
protein structure and its tendency to misfold using state-of-the-art
protein chemistry techniques.
Team members will also study the course and severity of brain
disease in mice that lack various types of genes and that are inoculated
with scrapie (the sheep version of transmissible spongiform encephalopathies).
“These studies will test the ability of a whole range
of genes to alter the development and progression of prion-triggered
diseases,” says Jirik.
Jirik is optimistic that his multidisciplinary team of researchers
will achieve important new insights into the causes and factors that
control the progression of prion diseases – insights that will one day
lead the way to potential treatments.
The Mouse Prion Initiative is a three-year program supported by the Alberta Agricultural Research Institute and the National Centers of Excellence:
Genetic Diseases Network. University of Calgary researchers from faculties across campus include Drs. Frank Jirik, Janice E.A. Braun, James C. Cross,
Roy A. Gravel, Richard Hawkes, Keith Sharkey, Michael Surette, Hans J. Vogel, Samuel Weiss and Gerald Zamponi. Researchers from the University
of Lethbridge include Dr. Bryan Kol, the University of British Columbia, Dr. Blair R. Leavitt, and from the University of Alberta, Dr. Christopher Power.