Montreal, QC – In recently published articles in PLoS Genetics and Biochimica Biophysica Acta, Benoit Coulombe, director of the Gene Transcription and Proteomics research unit at the institut de recherches cliniques de Montréal (IRCM), and his team have proposed 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.
The genetic code acts as a guide for creating the human body’s proteome from DNA, and “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 an article 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.”