Harrison, Joe - University of Calgary - Department of Biological Sciences

个人简介

PhD - Microbial Biochemistry University of Calgary, 2008 BSc University of Calgary, 2003

研究领域

My research involves the study of surface-attached bacterial communities called biofilms. Infectious bacterial biofilms have caught the eye of microbiologists because they are intrinsically resistant to antibiotic therapy and to immune clearance. Because biofilms are involved in many chronic and device-associated infections, it is imperative that we better understand the factors that contribute to their resistance to treatment and evasion of the immune system. My laboratory uses molecular genetics, genomics, biochemistry and experimental evolution to investigate two important aspects of biofilm microbiology. One aspect of my research program is to understand how bacteria in biofilms can establish chronic infections. I am particularly interested in Pseudomonas aeruginosa, a bacterium that makes biofilms in the airways of patients with the genetic disease cystic fibrosis (CF). These chronic infections will ultimately claim the lives of most CF patients and there is no known antibiotic therapy that can eradicate them. My program seeks to understand how intertwined processes of biofilm signal transduction, ecology and evolution are linked to the changes in bacterial virulence associated with chronic infections. P. aeruginosa is an ideal model for studying this problem because it is a pervasive hospital pathogen, it can be genetically manipulated, and it causes complications to CF treatment which alone may cost as much as sixty million dollars annually to Canadians. A second aspect of my research is focused on understanding how biofilms can withstand antimicrobial treatments and aims to devise new strategies to control them. This research utilizes Escherichia coli, a well-studied model organism that has informed nearly all aspects of basic and applied microbiology. This work aims to unravel the molecular mechanisms that generate physiological diversity in biofilms and seeks to identify the signaling and metabolic pathways that enable subpopulations of cells in biofilms to escape antimicrobial toxicity. The long term goal is to leverage a deep understanding of biofilm resistance mechanisms to identify parts of biofilms that may be selectively targeted for disruption.

近期论文

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Laura R Hmelo, Bradley R Borlee, Henrik Almblad, Michelle E Love, Trevor E Randall, Boo Shan Tseng, Chuyang Lin, Yasuhiko Irie, Kelly M Storek, Jaeun Jane Yang, Richard J Siehnel, P Lynne Howell, Pradeep K Singh, Tim Tolker-Nielsen, Matthew R Parsek, Herbert P Schweizer and Joe J Harrison (2015) Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange. Nature Protocols 10:1820-1841. Zhao, K., B. S. Tseng, B. Beckerman, F. Jin, M. Gibiansky, J. J. Harrison, E. Luijten, M. R. Parsek and G. C. Wong (2013). Psl trails guide exploration and microcolony formation in Pseudomonas aeruginosa biofilms. Nature 497:388-391. Lemire, J. A*., J. J. Harrison* and R. J. Turner (2013). Antimicrobial activity of metals: Mechanisms, molecular targets and applications. Nature Reviews Microbiology 11:371-384.. *Equal author contribution. Khakimova, M., H. G. Ahlgren, J. J. Harrison, A. M. English and D. Nguyen (2013). The stringent response controls catalases in Pseudomonas aeruginosa and is required for hydrogen peroxide and antibiotic tolerance. Journal of Bacteriology 195:2011-2020. Harrison, J. J., C. A. Stremick, R. J. Turner, N. D. Allan, M. E. Olson and H. Ceri (2010). Microtiter susceptibility testing of microbes growing on peg lids: A miniaturized biofilm model for high-throughput screening. Nature Protocols 5:1236-1254. Harrison, J. J., W. D. Wade, S. Akierman, C. Vacchi-Suzzi, C. A. Stremick, R. J. Turner and H. Ceri (2009). The chromosomal toxin gene yafQ is a determinant of multidrug tolerance for Escherichia coli growing in a biofilm. Antimicrobial Agents and Chemotherapy 53:2253-2258. Harrison, J. J., R. J. Turner, D. A. Joo, M. A. Stan, C. S. Chan, N. D. Allan, H. A. Vrionis, M. E. Olson and H. Ceri (2008). Copper and quaternary ammonium cations exert synergistic bactericidal and anti-biofilm activity against Pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy 52:2870-2881. Harrison, J. J., H. Ceri and R. J. Turner (2007) Multimetal resistance and tolerance in microbial biofilms. Nature Reviews Microbiology 5:928-938.