The invisible struggle that shapes the world
There is an endless struggle taking place on our planet that is invisible to the naked eye, yet shapes entire ecosystems and indeed life as we know it – the battle between bacteria and their viral predators, bacteriophages.
Bacteriophages are viruses that infect and destroy bacteria and are the most abundant and diverse biological entities on the planet, playing a significant role in maintaining the balance of the world’s ecosystems.
Bacteriophages can be both friends and foes. They act as friends when they suppress bacterial populations with harmful properties, including pathogenic bacteria. These phages could be extremely useful industrial and medical applications as biocontrol agents. Yet bacteriophages can also act as enemies because they can destroy “good” bacteria that play an important role in food and biotechnology fermentations. If the bacteria used to make cheese are neutralized by phages, for example, cheese production is destroyed.
Dr. Sylvain Moineau, Canada Research Chair in Bacteriophages and a professor at Université Laval's Faculty of Science and Engineering, is one of the world's leading experts on bacteriophages and curator of the world's largest public collection of them. Dr. Moineau and his team have been working for two decades on developing new tools that have led to a significant reduction of bacteriophage problems in dairy fermentations. They have also made several strides for their use as antibacterials in public health and in a wide variety of industries.
“Our main goal is to increase knowledge of phage biology,” he says. “We favor an integrative approach combining data from genomics, transcriptomics, proteomics, and structural biology to understand the interactions between phages and bacteria.”
His pioneer work on the interactions between bacteriophages and bacteria has also been fundamental to the discovery and understanding of the CRISPR-Cas system, a bacterial immune mechanism. Other scientists have recently used parts of the bacterial CRISPR-Cas system to develop a powerful gene editing tool that is currently revolutionizing research in life sciences.
After obtaining a bachelor’s degree in microbiology (1987), Sylvain Moineau completed a master’s degree (1990) and PhD (1993) in food sciences and technology at Université Laval. Following an industrial post-doc in the US, he returned to his alma mater in 1996. Since then, he is a professor of Microbiology in the Department of Biochemistry, Microbiology and Bioinformatics at the Faculty of Science and Engineering at Université Laval in Québec city.
In 2013, he obtained the NSERC Synergy Award, which recognizes a highly productive university-industry research partnership, which resulted in the development of a leading edge program to reduce the appearance of bacteriophages and preserve the high quality and typicity of Agropur cheeses. For the past three years, Dr. Moineau was named one of the World's Most Influential Scientific Minds for the second year running by strategic information company Thomson Reuters. In 2016 he received the Gloire de l’Escolle Medal, bestowed by the Université Laval alumni association and, most recently, the NSERC John C. Polanyi Award in 2017 for his CRISPR-Cas work.
Paving the way for genome modification
Dr. Moineau and his collaborators were the first to identify CRISPR-Cas as an immune system that protects bacteria from bacteriophages, in 2007. Among others, his team was the first to demonstrate in 2010 the workings of the CRISPR-Cas system, which targets and specifically cleaves the infecting bacteriophage's DNA. These groundbreaking discoveries opened the door to the use of CRISPR-Cas as a tool for genome editing and paved the way for a myriad of applications in life sciences.
“Despite its complicated name, the CRISPR-Cas9 technology is relatively simple and very effective at modifying the DNA of different cell types,” explains Dr. Moineau.
The technology is made up of two components: the CRISPR component (a small RNA molecule) acts as a GPS to recognize a very specific portion of a genome of interest and the Cas9 component is a protein that cuts DNA, like a molecular knife. When its genome is cut, a cell will quickly use its natural repair system to try to mend itself. But it’s possible to force the cell to repair the cut by providing a specific piece of DNA that would correct a mutation, create one or even add a new gene.
“We’d known since 1987 that bacteria carried a CRISPR-Cas system in their genome,” says Dr. Moineau, but it was only in 2007 that collaborators and our team demonstrated the biological function of the CRISPR-Cas system, which is actually a defense mechanism against foreign genetic elements such as viruses. In 2010, my lab showed that the CRISPR-Cas system cuts DNA.”
Other research teams around the world have run with some of Moineau’s landmark discoveries, including DNA recognition and cutting, to develop a tool to edit the genome.
“As a new genome modification technology, CRISPR-Cas9 heralds a revolution in biology and health science,” says Dr. Moineau. “It holds great promise for improving plant and animal production, or even perhaps to cure hereditary diseases.”
“It’s pretty unbelievable to think that we set out to make better cheeses and that, today, we could possibly treat people,” he says.