Alan R. Davidson

Alan R. Davidson

Professor

BSc, University of Toronto, 1983
PhD, University of Toronto, 1991
Postdoc, Massachusetts Institute of Technology, 1995

Address MaRS Centre, West Tower
661 University Ave., Room 1634
Toronto, ON
Toronto, ON M5G 1M1
Lab Davidson Lab
Lab Phone 416-978-8611
Office Phone 416-978-0332
Email alan.davidson@utoronto.ca

I first discovered the beauty and elegance of phages during my Ph.D. studies, which were focused on the DNA packaging enzyme of E. coli phage lambda. During my post-doctoral work at MIT, I switched to the field of protein structure and folding. I continued this work in my own lab investigating the thermodynamics and kinetics of folding of the SH3 domain. I have also worked extensively on the functioning of SH3 domains in budding yeast. Luckily, as time went on in my own lab, I was able to move back into the phage field.

In the News

Research Lab

My laboratory focuses on bacteriophages (phages), the viruses that infect bacteria. We investigate how phages work, and how we can exploit phage-derived entities for applications in human health. We also study anti-CRISPRs, which are phage-encoded inhibitors of CRISPR-Cas systems. We discovered these proteins, and are currently endeavouring to understand how they work, and how they can be exploited in genome editing applications.

Learn more: Davidson Lab

Research Description

Bacteriophages

My laboratory focuses on bacteriophages (phages), the viruses that infect bacteria. We are interested in:

  1. CRISPR-Cas systems. CRISPR-Cas systems are an adaptive immunity system in bacteria. They operate in a manner similar to RNAi in eukaryotes and are widespread in both bacteria and archaea. Recently CRISPR-Cas systems have been adapted for genome editing in a wide variety of species including humans. We discovered the first examples of phage-encoded genes that inhibit the CRISPR-Cas systems, including Cas9 systems used for genome editing. We are currently studying the prevalence of these anti-CRISPR systems, how they work, and their evolutionary impact.
  2. Phage-related entities encoded in bacterial genomes. These entities, such as R- and F-pyocins in P. aeruginosa or Photorhabdus Virulence Cassettes in other species, can mediate killing of other bacterial species or eukaryotic cells. Little is known of how these entities function. We aim to develop these phage-related entities into novel alternatives to antibiotics, tools for manipulating the microbiome, and agents for targeted treatment of human diseases.
  3. How phage particles assemble. For these studies we combine techniques of structural biology (X-ray crystallography, NMR, and electron microscopy) with molecular biology and in vivo studies.
  4. How phage genomes found within bacterial genomes (prophages) alter the physiology of the host bacteria. We pursue this work primarily in the pathogenic bacteria, Pseudomonas aeruginosa. We seek to understand how prophages affect virulence and pathogenesis of this organism. This work is relevant to Cystic Fibrosis patients in whom P. aeruginosa is a major cause of illness.

A major goal of my research program is to provide a fruitful training ground for my students where they can gain experience in as many techniques as possible, and develop independent projects based on their own interests and strengths.

Publications

View all publications on PubMed

Naturally occurring off-switches for CRISPR-Cas9
Pawluk, A., Amrani, N., Zhang, Y., Garcia, B., Hidalgo-Reyes, Y., Lee, J., Edraki, A., Shah, M., Sontheimer, E.J., Maxwell, K.L., Davidson, A.R.
Cell 167, 1829–1834 (2016).  Read

Inactivation of CRISPR-Cas systems by anti-CRISPR proteins in diverse bacterial species
Pawluk, A., Staals, R. H. J., Taylor, C., Watson, B. N. J., Saha, S., Fineran, P. C., Maxwell, K. L., and Davidson, A. R.
Nature Microbiology 13, 16085 (2016)  Read

Multiple mechanisms for CRISPR–Cas inhibition by anti-CRISPR proteins.
Bondy-Denomy, J., Garcia, B., Strum, S., Du, M., Rollins, M.F., Hidalgo-Reyes, Y., Wiedenheft, B., Maxwell, K.L., and Davidson, A.R.
Nature 526, 136–139 (2015).  Read

A new group of phage anti-CRISPR genes inhibits the type I-E CRISPR-Cas system of Pseudomonas aeruginosa
Pawluk A, Bondy-Denomy J, Cheung VH, Maxwell KL, Davidson AR.
MBio 25, e00896 (2014)  Read

HNH proteins are a widespread component of phage DNA packaging machines
Kala S, Cumby N, Sadowski PD, Hyder BZ, Kanelis V, Davidson AR, Maxwell KL
Proc Natl Acad Sci U S A. 111, 6022-6027 (2014)  Read

Bacteriophage genes that inactivate the CRISPR/Cas bacterial immune system
Bondy-Denomy, J., Pawluk, A., Maxwell, K.L. & Davidson, A.R.
Nature 493, 429–432 (2013)  Read

Structural and functional studies of gpX of Escherichia coli phage P2 reveal a widespread role for LysM domains in the baseplates of contractile-tailed phages
Maxwell KL, Fatehi Hassanabad M, Chang T, Paul VD, Pirani N, Bona D, Edwards AM, Davidson AR
J Bacteriol. 195, 5461-5468 (2013)  Read

Tail tip proteins related to bacteriophage λ gpL coordinate an iron-sulphur cluster
Tam, W., Pell, L.G., Bona, D., Tsai1, A., Dai, X.X., Hendrix, R.W., Maxwell, K.L., and Davidson, A.R.
J. Mol. Biol. 425, 2450–2462 (2013)  Read

Phages have adapted the same protein fold to fulfill multiple functions in virion assembly
Cardarelli, L., Pell, L.G., Neudecker, P., Pirani, N., Liu, A., Baker, L.A., Rubinstein, J.L., Maxwell, K.L., Davidson, A.R.
Proc Natl Acad Sci U S A 107, 14384-14389 (2010)  Read

The phage λ major tail protein structure reveals a common evolution for long-tailed phages and the type VI bacterial secretion system
Pell, L.G., Kanelis, V., Donaldson, L.W., Howell, P.L., Davidson, A.R.
Proc Natl Acad Sci U S A 106, 4160-4165 (2009)  Read