in Research Arena
OVC lab draws impressive funding, generates
valuable new knowledge
is the key to good research for, clockwise from top left,
Patricia Bell, Steven Raynard, Richard McCulloch, Prof.
Mark Baker, Leah Read and Erin Birmingham.
Photo by Martin Schwalbe
When you score a goal in hockey, almost everyone
can share the excitement. But find something unexpected
in the way mammalian cells control the homologous recombination
of chromosomes, and you may be the only one cheering for
But cheer they do in the OVC pathobiology lab headed by
Prof. Mark Baker,
where the goals-scored average has been pretty high of late.
Finding something that no one else has found before is a
real high, says Baker, even if there are a limited number
of people who can fully appreciate the significance.
You might say his lab has scored a hat trick recently in
terms of recognition in the scientific and medical communities.
The first goal came in the form of renewed funding from
the Canadian Institutes of Health Research (CIHR) and Natural
Sciences and Engineering Research Council (NSERC) that will
approach $1 million over the next five years.
The second relates to the publication this month of a paper
by Baker and lab technician Erin Birmingham in the prestigious
American Society for Microbiology (ASM) journal, Molecular
and Cellular Biology.
The third goal was scored by Baker's team at the Canadian
Society for Immunology meeting in April when their professional
colleagues applauded the complex analyses being done at
U of G.
Baker also scores his share of on-ice goals during pick-up
hockey in the U of G arena. He's manager and captain of
the Guelph Maple Leafs Red Team, who face off against the
White Team every Wednesday evening.
Hockey or research, this captain stresses the importance
of teamwork. He is one of seven people working in the recombination
lab at OVC. These scientists share an interest in the molecular
mechanisms of recombination and want to discover how it
is involved in the control of gene structure and function
and in the generation of human diseases, including cancer.
They are one of the few research teams in the world that
explore the fundamental biological process of homologous
An obscure concept to most of us, this basic process enables
changes to take place within the DNA of all living cells
and is vitally important in generating genetic diversity,
in adaptation and in the evolution of new species. Homologous
recombination is also a form of DNA repair that is important
during the growth of mammalian cells to prevent an accumulation
of mutations that could cause cancer and other diseases.
This is pure research, but there are obvious long-term
implications for human medicine through gene therapy and
for the growing biotechnology industry, says Baker. Every
biotech discovery and application that excites people today
had its roots at the very fundamental research level, he
Gene targeting is one example. During post-doctoral work
at the University of Toronto in the early 1980s, Baker worked
with mentor and U of T professor Marc Shulman on a research
team that was among the first to successfully develop a
technique for gene targeting in mammalian cells. Now it's
a routine process in many labs around the world, used to
introduce site-specific changes into the chromosomal genes
of living cells in an effort to precisely manipulate the
genome. This technology permits genes to be modified right
in their normal chromosomal environment, affording more
precise study of their function.
In applied terms, gene targeting has the potential to aid
the development of new strains of plants and animals and
may one day serve as an effective form of human gene therapy.
Baker continued his work in mammalian recombination at
the National Research Council's Biotechnology Research Institute
in Montreal from 1988 to 1990 and launched his recombination
lab at OVC when he joined U of G in 1990. Leah Read has
worked with him as a lab technician for 10 years; Birmingham,
for about four years.
The recombination team also includes current PhD candidates
Steven Raynard and Richard McCulloch and M.Sc. student Patricia
Bell. Prof. Julang Li completed post-doctoral work in the
lab before joining the faculty of the Department of Animal
and Poultry Science last summer. And there are almost always
two undergraduate students working in the lab on semester
projects. This summer, the lab has received funding from
NSERC and U of G to hire biomedical sciences student Cara
Reith and molecular biology and genetics student Shauna
Lee as research assistants.
Baker says it's important to offer research opportunities
to undergraduate students. "You have to teach people
how to do research - it's not intuitive. You have to teach
students how to think about science, how to ask the kinds
of questions that most people don't normally think about."
Recombination research requires good analytical skills,
tenacity and self-motivation, he says. "We do excellent
work, but are relatively unknown to most undergraduates.
A lot of our own undergraduate students here at U of G don't
appreciate the significance of the medical research being
done at this University."
In the major leagues, OVC's recombination lab is well respected.
CIHR and NSERC have provided operating funding and fellowship
support to Baker's research activities and graduate students
over the lab's 11-year lifetime.
"We've developed a unique system for studying the
complex processes involved in homologous recombination,"
says Baker. "Ours is one of a handful of labs worldwide
doing this level of investigation."
The paper being published in the ASM journal reports on
one of the important new findings by the Guelph team.
"Our results suggest that mammalian cells exert a
high level of control over how crossing over takes place
between two DNA sequences during homologous recombination,"
The naturally occurring exchange of genetic information
by crossing over was previously considered to happen randomly.
But Baker's team has found evidence that animal cells can
actually control how DNA exchanges occur, perhaps a deliberate
manoeuvre to prevent abnormal chromosome changes and, potentially,
large numbers of genetic mutations within a species.
"We are continuing our investigation of the crossing-over
process, how mismatches created during recombination are
repaired and how homologous recombination normally occurs
when there is no crossing over," he says.
Baker's lab is also studying the chromosomal immunoglobulin
locus, a region in the mammalian genome that is responsible
for the production of antibodies during an immune response.
Their evidence suggests that this locus resembles a recombination
"hot spot" in that it is capable of supporting
a high level of homologous recombination.
"Our understanding of how recombination hot spots
function is very limited," he says. "By studying
this particular locus, we hope to learn more about the mechanisms
that control this activity. We think this knowledge may
enlarge our understanding of how antibodies in the body
develop the characteristics needed to fight an invading
pathogen or what triggers the body's immune system to attack
itself in autoimmune diseases like multiple sclerosis, rheumatoid
arthritis and lupus. We're looking for a fundamental view
of how these processes happen to provide the base understanding
from which future applications for health care and industrial
uses can grow."