Genome Canada: Canadian Researchers Make Proteomics Breakthrough - Discovery Being Hailed As a Paradigm Shift in Biology.

Business Editors & Health/Medical Writers

A team of Canadian researchers has used a proteomics approach - the study of protein location, interaction, structure and function - and discovered a cellular process that sheds new light on how pathogens cause infection in humans. This could lead to new treatments for infectious diseases such as tuberculosis and Salmonella infection. (see attached backgrounder for more information)

Dr. Michel Desjardins and his team say that this research - funded by Genome Canada/Genome Quebec, Caprion Pharmaceuticals and CIHR - found a new cellular process that challenges the current text book view stipulating that phagosomes, the organelles that internalize infection-causing microorganisms into cells, are formed by the invagination of the plasma membrane. Instead, much of the membrane used to form phagosomes comes from the endoplasmic reticulum, which is normally involved in the synthesis of proteins inside the cell. This unexpected finding identifies a new mechanism of entry for microbes in our cells.

"Infection by intracellular pathogens is like burglars entering our house," said team leader Dr. Michel Desjardins of the Universite de Montreal and Director of Proteomics at Caprion Pharmaceuticals. "While we equip our front door with sophisticated anti-theft devices, we suddenly realize they are entering through the back door." Identification of the endoplasmic reticulum as the entry door for microbes into our cells allows the development of new therapeutic approaches to fight infectious diseases.

The team's research, which is published in the July 12th issue of the prestigious scientific journal Cell, is being hailed as a paradigm shift in biology due to the emerging science of proteomics.

"To fully understand how the human body works, we not only need to study the functions of our genes, but also the functions of our proteins," said Genome Canada President Dr. Martin Godbout. "This is a job a thousand times bigger than the sequencing of the human genome, but a sector in which Canada is, as demonstrated by today's announcement, definitely playing a leadership role."

While the completion of the Human Genome Project opened the door for new scientific discoveries, it does not reveal the cause of a disease, nor does it identify specific targets for treatment. Proteomics aims to identify and characterize the proteins present in normal and diseased biological samples, enabling researchers to design the next generation of novel drugs and treatments.

"We are particularly proud of the proteomics breakthrough achieved by Dr Desjardins and his team," said Mr. Paul L'Archeveque, President and Chief Executive Officer of Genome Quebec. "This fully supports our innovation strategy that allows Quebec researchers to contribute to sciences and research progress on the international scene."

"In order to treat a disease in the most effective way possible, it is necessary to understand the manner in which proteins function," said CIHR Vice-President Dr. Mark Bisby "This important new concept uncovered by Dr. Desjardins and his team will help to develop an entirely new generation of drugs to combat disease directly, transforming our health care system for the benefit of all Canadians."

"Caprion continues to strengthen its leadership position in the field of proteomics by collaborating with preeminent research organizations," said Dr. Daniel Chelsky, EVP & Chief Scientific Officer of Caprion Pharmaceuticals. "Dr. Desjardins' work illustrates how a comprehensive analysis of organelle proteomes, such as that used at Caprion, leads to important new knowledge and commercializable discoveries."

Dr. Desjardins is supported in his work by Genome Canada/Genome Quebec, Caprion Pharmaceuticals Inc, and the Canadian Institutes of Health Research.

About Genome Canada and Genome Quebec

Genome Canada is the primary funding and information resource relating to genomics and proteomics in Canada. It has received $300 million from the Government of Canada in order to develop and implement a national strategy in genomics and proteomics research for the benefit of all Canadians in key selected areas such as agriculture, bioinformatics, environment, fisheries, forestry, health and technology development. To date, Genome Canada has invested more than $290 million across Canada, which, when matched by other funding, amounts to $580 million in 56 innovative genomics research projects. Genome Quebec is a not-for-profit investment organization created to stimulate genomics and proteomics research initiatives in Quebec. Beyond Genome Canada's support, Genome Quebec is also benefiting from $40 million in funding from the Ministere de la Recherche, de la Science et de la Technologie du Quebec. Genome Quebec's mission is to play a structuring and mobilizing role in the important field of genomics. Its funding formula calls for investments by the private (venture-capital companies and biotech and pharmaceutical corporations), and public sectors alike.

About Caprion Pharmaceuticals

Caprion is a privately held drug discovery company applying proteomics to discover and develop innovative products for the diagnosis and treatment of disease. CellCarta(TM), Caprion's proprietary subcellular proteomics platform, maps the proteomes of organelles isolated from healthy and diseased tissue to uncover protein variations associated with disease. From these protein maps, Caprion identifies clinically relevant drug targets and functional insights for drug development in areas such as cancer, metabolic disorders, and infectious diseases. The Company also has partnered products for Mad Cow Disease and variant Creutzfeldt-Jacob Disease diagnostics, in development with IDEXX Laboratories and Ortho-Clinical Diagnostics. For more on Caprion, see www.caprion.com.

About CIHR

CIHR is Canada's premier agency for funding health research. Its objective is to excel, according to internationally accepted standards of scientific excellence, in the creation of new knowledge and its translation into improved health for Canadians, more effective health services and products, and a strengthened health care system.

About Universite de Montreal

Universite de Montreal is a leader among major research universities. With its two affiliated schools, the Ecole Polytechnique and the Ecole des HEC, its campus is the largest in Quebec. It offers undergraduate, masters and doctoral level programs in almost all areas of knowledge, has more than 50,000 students and awards more than 2,500 master's and doctorate degrees every year. It ranks second among universities in Canada in terms of research funding and research grants per professor. Universite de Montreal is committed to developing new knowledge and transmitting existing expertise.

PROTEOMICS AND INFECTION BY INTRACELLULAR PATHOGENS BACKGROUNDER

Many infectious diseases are caused by the entry of microbes into white blood cells called macrophages that are part of our immune system. It is thought that the microbes accomplish this entry by invaginating (folding in of an outer layer so as to form a pocket in the surface) the cell surface, or plasma membrane, in organelles called phagosomes that form around the microbe.

A significant part of the membrane used to form the phagosome in macrophages has now been shown to come from the endoplasmic reticulum (ER), a membrane system that is involved in the synthesis of proteins inside the cell. Phagosomes are formed by direct fusion of ER to the plasma membrane in a process called phagocytosis. The process acts as a "Trojan horse" to permit infection-causing microbes to survive in host cells.

Dr. Michel Desjardins of the Universite de Montreal and his team, who conducted the research, carried out a comprehensive characterization of the composition of phagosomes using a proteomics approach that led to the identification of more than 250 proteins, including proteins of the ER called calnexin and calreticulin.

It was previously thought that phagocytosis involved solely the plasma membrane, and it is due to new understanding of proteomics that the researchers were able to propose a new look at phagocytosis.

Identifying the ER as an integral part of the phagosome membrane could lead to new strategies and drugs for preventing and treating infection and new ways to promote phagosome maturation without the intrusion of infectious microbes.

Proteomics - the study of the location, interaction, structure, and function of proteins - aims to identify and characterize the proteins present in normal and diseased tissues. Proteins regulate the activities of cells, tissues, and organs, and interactions between them can trigger chemical reactions within cells. Abnormalities in protein production or function have been connected to many diseases and health conditions, including cancer, AIDS, and depression. The ability to modulate proteins is an attractive target for designing drugs to treat these diseases and conditions.

The study of the human genome has resulted in much new knowledge. But while the genetic code is significant, it does not provide a comprehensive understanding of the cause of a disease, nor does it identify specific targets for treatment.

This research takes proteomics a step further by going beyond the generation of "lists" of proteins and placing each protein in a biological context.