(1) Finding new phages: Phages are ubiquitous, and an old adage in phage biology is that if you can culture a bacterium, you can find phages for it. However, until recently, the microbes in the gut were largely considered unculturable. Recent breakthroughs in bacterial culturing spearheaded by another Farncombe Institute research group, the Surette lab, have enabled a new exploration of the microbiome. For us, as collaborators, this is a unique opportunity to isolate never-before-seen phages, with all of the exciting potential for discovery that entails. We’re particularly interested in bringing new techniques (and technology) to the process of phage discovery and characterization, as traditional phage isolation is largely based on a 100-year old technique.
Some highlights in phage discovery research: the discovery of crAssphage (2014), the autolykiviridae (2017). Working on aspects of this project: Dr. Chavez-Carbajal, Gayatri Nair, Rachelle Szymkiewicz.
(2) Phages as good house-guests: When a phage goes dormant within a host, this is a kind of symbiosis. The phage ties its fate to that of its host, and has a vested interest in its host's continued survival. Unsurprisingly, then, phages modify the cell they reside in to better suit their purposes - often granting their host protection from other phages, or, famously, enabling the production of new toxins. As such, phages can manipulate bacterial communities both by culling some members and helping others. We’re tackling the role of phages ‘as friends’ to bacteria on both a community level - to see whether phages help stabilize bacterial communities - and with select bacteria of interest that harbour dormant phages.
Some highlights in phage-mediated host fitness: Fitness of lambda lysogens (1975), phage-mediated "sustainable farming" of their hosts (2015). For a related ecological perspective on growing gut bacterial communities, check out Dr. Emma Allen-Vercoe's research group. Working on aspects of this project: Felix Croteau, Tamina Jose.
(3) Manipulating phage behaviour: Many phages lie dormant in their hosts. These phages can be awakened (induced) by environmental signals such as chemical stressors and radiation. It's becoming increasingly apparent that phages can respond to a wider range of signals, including from other phages! In partnership with the McMaster HTS lab, we're working to find new signals that can modify the behaviour of phages. These will help us discovery new phages (Project 1) but also identify factors that could impact our microbiome in a phage-mediated manner. We’re also looking at ways to exploit signals phages respond to, in order to drive shifts in bacterial populations in a therapeutic context.
(4) Phage resistance: Every phage-bacterium interaction - and all of the above 3 projects - are subject to a constant arms race between bacteriophages and their hosts. Whether it’s looking for new mechanisms of resistance, evaluating the impact of phages resistance on the behaviour/fitness of the host, or approaching phage resistance as a question faced by bacterial populations (and not simply individuals), findings from all our other projects are constantly generating new avenues of inquiry for exploring phage resistance.
Some highlights in Phage resistance work: the discovery of the CRISPR-Cas adaptive immune system in bacteria (2007), systematic discovery of new anti-phage systems (2018), shared elements of eukaryotic and prokaryotic immune systems (2019). Working on aspects of this project are: Breanna Landry, Janice Tai, Kevin Zhao.
(5) Bacterial Synergy: You can never predict where curiosity-driven research will take you, and even projects that start with phages might take us down other paths, if we’re willing to follow them! As we’ve been updating 100-year old techniques for phage discovery (Project 1), we’ve also stumbled upon new and exciting bacterial phenotypes in those same assays. In particular, we’ve detected the expression of previously uncharacterized virulence factors in the commensal bacterial genus Bacteroides that are only expressed as a result of a synergistic interaction between distinct isolates. Working on this project are: Hiba Shareefdeen, Brandon Ly.