Alexander P. Hynes, PhD
Farncombe Family Chair in Phage Biology
Assistant Professor, Department of Medicine
Health Sciences Centre – 3N8 D
1280 Main Street West Hamilton, ON Canada L8S 4K1
Bacteriophages (phages) are viruses that specifically infect bacteria. Phages are ubiquitous, and the rule of thumb is that for every bacterium there are 10 phages. Consequently, phages are responsible for the death of an estimated >20% of the global bacterial population every day. Their influence on bacterial populations isn’t limited to predation – ‘temperate’ phages integrate into their host’s genome and can drastically impact the physiology of the bacteria they infect, protecting them from other phages, encoding new surface proteins or bacterial toxins, and conferring numerous fitness advantages to their hosts.
My group’s research focuses on establishing the role of phages in shaping key bacterial populations, notably those of the gut microbiome. In this environment, temperate phages are common and diverse, and changes in phage populations correlate closely with disease states. A better characterization of these phage communities will allow us to identify new diagnostic and predictive markers, as well as develop phage-based approaches to manipulate the gut microbiome.
Current Research Topics
Isolation of new gut-associated bacteriophages. An old adage in phage biology is that if you can culture a bacterium, you can find phages for it – but, until recently, the gut microbiome was largely considered unculturable. We have access to a large collection of cultured gut microbiome isolates whose phage diversity is unexplored. My group is also developing new high-throughput methods of isolation that will aid in the identification of phages associated with disease states.
Exploring the role of phages in shaping bacterial populations. With new temperate phages, we evaluate the direct impact of the integrated phage on the physiology of its host (e.g. competitive fitness, phage susceptibility) as well as on its role within bacterial communities. Furthermore, we are working to build model stable phage communities in mice, in order to directly assess the impact of disrupting the phages of a bacterial community.
Tracking phage populations and disease. Phage abundance and diversity in the gut correlate with disease states. By tracking phage populations in patients suffering from gut dysbiosis leading to disease, especially as they undergo treatment (e.g. faecal microbiota transplants, antibiotic treatments), we’re working towards establishing a causal relationship between keystone phage species and a healthy microbiome.
- Hynes, AP, Rousseau, GM, Lemay, ML, Horvath, P, Romero, DA, Fremaux, C et al.. An anti-CRISPR from a virulent streptococcal phage inhibits Streptococcus pyogenes Cas9. Nat Microbiol. 2017;2 (10):1374-1380. doi: 10.1038/s41564-017-0004-7. PubMed PMID:28785032 .
- Hynes, AP, Moineau, S. Phagebook: The Social Network. Mol. Cell. 2017;65 (6):963-964. doi: 10.1016/j.molcel.2017.02.028. PubMed PMID:28306511 .
- Hynes, AP, Lemay, ML, Trudel, L, Deveau, H, Frenette, M, Tremblay, DM et al.. Detecting natural adaptation of the Streptococcus thermophilus CRISPR-Cas systems in research and classroom settings. Nat Protoc. 2017;12 (3):547-565. doi: 10.1038/nprot.2016.186. PubMed PMID:28207002 .
- Hynes, AP, Shakya, M, Mercer, RG, Grüll, MP, Bown, L, Davidson, F et al.. Functional and Evolutionary Characterization of a Gene Transfer Agent's Multilocus "Genome". Mol. Biol. Evol. 2016;33 (10):2530-43. doi: 10.1093/molbev/msw125. PubMed PMID:27343288 PubMed Central PMC5026251.
- Hynes, AP, Lemay, ML, Moineau, S. Applications of CRISPR-Cas in its natural habitat. Curr Opin Chem Biol. 2016;34 :30-36. doi: 10.1016/j.cbpa.2016.05.021. PubMed PMID:27280696 .
- Hynes, AP, Labrie, SJ, Moineau, S. Programming Native CRISPR Arrays for the Generation of Targeted Immunity. MBio. 2016;7 (3):. doi: 10.1128/mBio.00202-16. PubMed PMID:27143383 PubMed Central PMC4959665.
- Hynes, AP, Villion, M, Moineau, S. Adaptation in bacterial CRISPR-Cas immunity can be driven by defective phages. Nat Commun. 2014;5 :4399. doi: 10.1038/ncomms5399. PubMed PMID:25056268 .
- Hynes, AP, Mercer, RG, Watton, DE, Buckley, CB, Lang, AS. DNA packaging bias and differential expression of gene transfer agent genes within a population during production and release of the Rhodobacter capsulatus gene transfer agent, RcGTA. Mol. Microbiol. 2012;85 (2):314-25. doi: 10.1111/j.1365-2958.2012.08113.x. PubMed PMID:22640804 .
- Fogg, PC, Hynes, AP, Digby, E, Lang, AS, Beatty, JT. Characterization of a newly discovered Mu-like bacteriophage, RcapMu, in Rhodobacter capsulatus strain SB1003. Virology. 2011;421 (2):211-21. doi: 10.1016/j.virol.2011.09.028. PubMed PMID:22018635 .
- Tremaroli, V, Workentine, ML, Weljie, AM, Vogel, HJ, Ceri, H, Viti, C et al.. Metabolomic investigation of the bacterial response to a metal challenge. Appl. Environ. Microbiol. 2009;75 (3):719-28. doi: 10.1128/AEM.01771-08. PubMed PMID:19047385 PubMed Central PMC2632130.