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Researchers at Mass. General, University
of Montreal create model of key immune-system component
Protein interaction model may lead
to better understanding of infectious disease processes
BOSTON - December 8, 2006 - Researchers at Massachusetts
General Hospital and the University
of Montreal, along with colleagues at Johns
Hopkins School of Medicine, have made a major breakthrough in
understanding an essential aspect of the immune system. For the
first time, using a systems biology approach, they have developed
a model that facilitates study of the function of the phagosome.
The phagosome is the organelle responsible for the destruction of
infectious pathogens that cause such diseases as tuberculosis and
salmonellosis, as well as those that could be used in bioterrorism.
The results of their study were published this week in the journal
Nature.
Infectious diseases remain one of the main causes of death in the
world, and the phenomenon of antibiotic resistant bacteria worsens
the situation each year. Thanks to the model developed by teams
led by Michel Desjardins, PhD, Department of Pathology and Cellular
Biology, University of Montreal; Lynda Stuart, MBBS, and Alan Ezekowitz,
MBChB; Laboratory of Developmental Immunology, Massachusetts General
Hospital; and Joel Bader, PhD, Biomedical Engineering Laboratory,
Johns Hopkins University, it will now be possible to better understand
the complex interactions that govern the functioning of the phagosome.
"We have taken a crucial step here," Desjardins explains.
"We can now reach a better understanding of the molecular processes
involved in infections by using a global approach based on proteomics
and genomics. This approach will expedite development of therapies
and the production of new vaccines. The major investments made in
recent years in proteomics research in Québec and Canada
have enabled us to pool our resources and apply promising new approaches
like systems biology." Desjardins is associate professor of
Pathology and Cellular Biology and holds the Canada Research Chair
in Cellular Microbiology at the University of Montreal.
As Stuart explains, "Phagocytes are immune system cells that
internalize, kill, and digest bacteria within an intracellular compartment
called the phagosome, a major battleground in the host-pathogen
conflict. Despite its important role in our normal immune defense,
the organization and functioning of the phagosome are poorly understood."
By analyzing a cell line of phagocytes from the Drosophila
fruit fly, a common biological model, the researchers identified
more than 600 proteins that may be involved with the operation of
the phagosome. They then constructed a detailed map of the interactions
among these proteins and were able to identify previously unknown
regulators of phagocytosis and potential molecular pathways of immune
defense.
"Phagocytosis is very similar in many organisms, so we are
able to learn about this process by studying it in simpler organisms,
such as Drosophila," Stuart continues. "By combining
classic cell biology with the newer approaches of proteomics, functional
genomics and computational analysis, we have generated a model that
we believe will facilitate our understanding of infectious diseases
and expedite the development of new strategies to fight pathogens."
Stuart is an instructor in Pediatrics at Harvard Medical School.
Ezekowitz is now at Merck Research Laboratories in Rahway, N.J.
"It is exciting to see that systems biology has the power to
unravel how the phagosome works by revealing the intricately woven
roles of all the molecules involved in killing infectious agents,"
says Bader, who is an assistant professor of Biomedical Engineering
and a member of the High-Throughput Biology Center at Hopkins. The
study was supported by grants from the Wellcome Trust and the U.S.
National Institutes of Health, Genome Québec, Genome Canada,
and the Canada Institutes of Health Research (CIHR).
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of nearly $500 million and
major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, transplantation biology and photomedicine. MGH and Brigham
and Women's Hospital are founding members of Partners HealthCare
HealthCare System, a Boston-based integrated health care delivery
system.
Media Contacts: Sue
McGreevey, MGH Public Affairs
Sophie Langlois,
University of Montreal
Physician Referral Service: 1-800-388-4644
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