Wednesday, April 3, 2013
Benoit Coulombe’s team defines the “chaperone code” creating new hopes for the treatment of degenerative diseases
Benoit Coulombe, Director of the Gene Transcription and Proteomics research unit at the IRCM, and his team propose a new code in biology. The existence of this “chaperone code” is redirecting research efforts and creating new hopes for the treatment of degenerative diseases.
Human cells function thanks to a multitude of proteins grouped together into an army of small molecular machines that carry out all functions necessary to life. We often refer to these protein machines as a whole as the “proteome”. The genetic code acts as a guide for creating these protein machines from DNA.
“The resulting proteins are not yet functional or active,” says Dr. Coulombe. “They must first be folded into their three-dimensional structures and assembled into machines capable of performing their actions. It has been demonstrated that a series of specialized proteins, called “molecular chaperones”, carry out this vital function.”
Several degenerative diseases are caused by defects in protein folding, which often result from abnormal activity in molecular chaperones. While attempting to better understand how molecular chaperones function, the IRCM research team published one of the key articles in the field in the scientific journal PLoS Genetics.
“We identified a family of modification enzymes (named “methyltransferases”) that target and regulate chaperones,” explains Philippe Cloutier, research assistant in Dr. Coulombe’s laboratory. “This discovery indicates that the posttranslational modification (PTM) of chaperones plays an important role in controlling their activity. PTM is the addition of a chemical group to a protein, thereby causing a change in the protein’s function.”
“Encouraged by this discovery, we then analyzed nearly 200 articles published in scientific literature on the role of chaperone modification,” adds Philippe Cloutier. “Results of our analysis were recently published in the scientific journal Biochimica Biophysica Acta.”
As a result of this discovery and the analysis of the scientific articles, the IRCM’s team is proposing the existence of a code that regulates the activity of chaperones. This code, named “chaperone code” by the team, consists in various modification arrangements that would control the function of chaperones according to the cells’ needs.
“Just as the genetic code stipulates how to make proteins from our genes’ DNA, the chaperone code would specify how to produce functional proteins by orchestrating their folding and assembly into active molecular machines,” explains Dr. Coulombe.
“The existence of such a code regulating the activity of chaperones is redirecting research efforts, because a better understanding on this code could provide us with new weapons to fight various degenerative diseases,” concludes Dr. Coulombe. “Decrypting the chaperone code is currently my laboratory’s top priority. It offers promising possibilities to reverse cell and tissue degeneration associated with numerous diseases.”
"These findings identify a previously unknown way of regulating a particular chaperone that has been linked to the disease ALS (amyotrophic lateral sclerosis or Lou Gehrig’s disease) and to another rare neuromuscular degenerative disease,” says Dr. Paul Lasko, Scientific Director of the CIHR Institute of Genetics. “This opens up a new approach for targeting therapies against these and potentially other related disorders. CIHR is pleased to support Dr. Coulombe and his team and wishes them continued success in their research."
About the research projects
Research at the IRCM was funded by the Canadian Institutes of Health Research (CIHR) and the Fonds de recherche du Québec – Santé as part of the Projects for innovative strategic development.
About Benoit Coulombe
Benoit Coulombe obtained a PhD in molecular biology from the Université de Montréal. He is Full IRCM Research Professor, Director of the Gene Transcription and Proteomics research unit, Director of the Proteomics Discovery Platform, and Director of the National platform for human interactome mapping. Dr. Coulombe is also full research professor in the Department of Biochemistry at the Université de Montréal. For more information, visit www.ircm.qc.ca/coulombe
About the IRCM
Founded in 1967, the Institut de recherches cliniques de Montréal (www.ircm.qc.ca
) is currently comprised of 35 research units in various fields, namely immunity and viral infections, cardiovascular and metabolic diseases, cancer, neurobiology and development, systems biology and medicinal chemistry. It also houses three specialized research clinics, eight core facilities and three research platforms with state-of-the-art equipment. The IRCM employs 425 people and is an independent institution affiliated with the Université de Montréal. The IRCM Clinic is associated to the Centre hospitalier de l’Université de Montréal (CHUM). The IRCM also maintains a long-standing association with McGill University. The IRCM is funded, in part, by the Quebec ministry of Higher Education, Research, Science and Technology.
About the Canadian Institutes of Health Research (CIHR)
CIHR is the Government of Canada's health research investment agency. CIHR's mission is to create new scientific knowledge and enable its translation into better health, more effective health services and products, and a stronger Canadian health care system. Composed of 13 Institutes, CIHR provides leadership and support to more than 14,100 health researchers and trainees across Canada.
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For more information and to schedule an interview with Dr. Coulombe, please contact:
Communications Officer (IRCM)
Communications Director (IRCM)