(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.
Some highlights in phage discovery research worldwide: the discovery of crAssphage (2014), the autolykiviridae (2017)
(2) Phage perception: 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've embarked upon a more systematic characterization of signals inducing phages. We are working to generate a library of induction compounds that will aid in finding new phages, as well as identify factors that could impact our microbiome by driving a shift in the behaviour of its phages.
Some highlights in Phage perception work worldwide: phage communication (2017)
(3) Phages as Friends: 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. We're particularly interested in phages that confer fitness benefits to their host, which we measure by co-culturing infected and uninfected cells under a variety of conditions and observing who dominates the competition.
Some highlights in phage-mediated host fitness: Fitness of lambda lysogens (1975), phage-mediated "sustainable farming" of their hosts (2015).
(4) Phage Transplants: Fecal microbiota transplants (FMTs) aim to restore a healthy microbiome by transfering feces from a healthy donor to a patient suffering from a disease associated with a dysbiosis in the gut. These treatments work well for C. difficile infections as well as showing promise for the treatment of Ulcerative colitis. Curiously, they have generally not led to convincing detectable “engraftment” of the donor microbiome in the recipient. We are working to track phage populations through treatment of ulcerative colitis to see if they are being transplanted, and, if they are, to tease apart their contribution to patient outcomes.
The lab only opened its doors on January 2nd 2018, and is rapidly ramping up capacity and infrastructure. As equipment grants come through, we'll be exploring a number of other projects.
A Healthy Phageome: The recent notion of a "Healthy phageome" is that there is a phage population in balance with (or balancing) your microbiome. This project is expected to get underway in late 2018, pending an equipment grant for bioreactors. For a related ecological perspective on growing gut bacterial communities, check out Dr. Emma Allen-Vercoe's research group.
CRISPR-Cas Immunity: Dr Hynes has worked extensively on the CRISPR-Cas system as a bacterial anti-phage adaptive immune system. He maintains an active interest in the field, but acknowledges that it's a field that moves so quickly that as a new research group, he has to first build a solid base of trainees with phage expertise to be able to contribute to that exciting field again. He intends to revisit his CRISPR-based project ideas in mid-2019.