I was trying to decide on a major subject after I was accepted into the B.Sc. program at the University of Alberta. I was always good at the sciences such as math, physics, chemistry and biology, but could not decide which one subject to major in. Then it occurred to me one evening while listening to music that perhaps I should learn something new, and I knew absolutely nothing about genes, DNA, regulation etc, It was 1972 and the revolution in molecular biology and genetic research had just begun. So I majored in genetics for my B.Sc. degree and followed with a Ph.D. degree in genetics. I learned about how to manipulate DNA (cloning and sequencing) and how genes are regulated. When I came to the Department of Microbiology at the University of Guelph, I knew very little about microbiology and have to learn pretty well from scratch. Luckily, DNA is the same regardless where they came from. Hence, I was able to use my knowledge on DNA to study virulence and pathogenesis of microbs.
The research in my laboratory can be divided into two directions, basic research and applied research. We studied a bacterium Mannheimia haemolytica that causes pneumonic pasteurellosis in cattle, commonly called shipping fever. The bacterium is a commensal in nasal passages of healthy animals. When the animals are stressed, their immune system is depressed and cannot remove the bacterium inhaled into the lungs. The bacterium colonize the lungs, produce toxic molecules that damage the lung tissue, leading to pneumonia. We have cloned and sequenced a collection of genes coding for various virulence factors of the bacterium. By characterizing each of these virulence factors, we are building a better understanding of the pathogenesis of this bacterium and the disease. In addition to studying the virulence genes of M. haemolytica, we are studying the mechanisms of gene regulation, ie. what and determines when these virulence genes are expressed. One of the approaches is to examine in vivo expressed genes. Since calves are the natural host of the bacterium, we have infected animals with the bacterium to cause pneumonia and re-isolated the bacterium from pneumonic lungs. RNA is extracted directly from these bacterium and used for RT-PCR analysis of in vivo expressed genes. A DNA microarray of M. haemolytic is also being designed to study global expression of genes.
On the applied research, I have a collaborative research to develop an edible vaccine to protect cattle from shipping fever by the construction of transgenic plants expressing some of the important antigens that we have characterized. The DNA from each of the selected antigen is introduced into alfalfa by Agrobacterium tumefaciens mediated transformation. After the transgenic plants have been characterized, they will be grown in large quantities for feeding trials in calves. We expect to create four to five transgenic lines, each producing a different antigen of M. haemolytica for use as a mixture in an edible vaccine.
Orouji, S., D.C. Hodgins, R.Y.C. Lo, and P.E. Shewen. (2012) Serum IgG response in calves to the putative pneumonic virulence factor Gs60 of Mannheimia haemolytica. Can J. Vet. Res. In the Press.
Sathiamoorthy, S., P.E. Shewen, D.C. Hodgins, and R.Y.C. Lo. (2012) in vivo gene expression in Mannheimia haemolytica A1 during a time-course trial in the bovine host. Vet. Microbiol. 158: 163-171.
Inamoto, I., and R.Y.C. Lo. (2011) A proteomic analysis of the regulon of the NarP two-component regulatory system response regulator in the bovine pathogen Mannheimia haemolytica A1. BMC Research Notes 4: 510
Sathiamoorthy, S., D.C. Hodgins, P.E. Shewen, S.K. Highlander, and R.Y.C. Lo. (2011) A snap-shot of Mannheimia haemolytica A1 gene expression during infection in the bovine host. FEMS Microbiol. Letts. 325: 148-154.
Inamoto, I., and R.Y.C. Lo. (2010) Identification of putative two-component regulatory systems in the bovine pathogen Mannheimia haemolytica A1, and preliminary characterization of the NarQ/P system. FEMS Microbiol. Letts. 311: 27-35.
Wong, H., L. Louie, R.Y.C. Lo, and A.E. Simor. (2010) Characterization of Staphylococcus aureus isolates with partial and complete absence of Staphylococcal Cassette Chromosome Elements. J. Clin. Microb. 48: 3525-3531.
Daigneault, M. C., and R.Y.C. Lo. (2009) Analysis of a collagen-binding trimeric autotransporter adhesin from Mannheimia haemolytica A1. FEMS Microbiol. Letts. 300: 242-248.
Wong, H., L. Louie, C. Watt, E. Sy, R.Y.C. Lo, M.R. Mulvey, and A.E. Simor. (2009) Characterization of ermA in macrolide-susceptible strains of methicillin-resistant Staphylococcus aureus. Antimicrob. Agents and Chemoth. 53: 3602-3603.
Lee, R.W.H., M. Cornelisse, A. Ziauddin, P.J. Slack, D.C. Hodgins, J.N. Strommer, P.E. Shewen, and R.Y.C. Lo. (2008) Expression of a modified Mannheimia haemolytica GS60 outer membrane lipoprotein in transgenic alfalfa for the development of an edible vaccine against bovine pneumonic pasteurellosis. J. Biotech. 135: 224-231.
Lo, R.Y.C., and L. Sorensen. (2007) The outer membrane protein OmpA of Mannheimia haemolytica A1 is involved in the binding of fibronectin. FEMS Microbiol. Letts. 274: 226-231.
Lo, R.Y.C., S. Sathiamoorthy, and P.E. Shewen. (2006) Analysis of in vivo expressed genes inMannheimia haemolyticaA1. FEMS Microbiol. Letts. 265: 18-25.
Gioia, J., X. Qin, H. Jiang, K. Clinkenbeard, R.Y.C. Lo, Y. Liu, G.E. Fox, S. Yerrapragada, M.P. McLeod, T.Z. McNeill, L. Hemphill, E. Sodergren, Q. Wang, D.M. Muzny, F.J. Homsi, G.M. Weinstock and S.K. Highlander. (2006) The genomic sequence of Mannheimia haemolytica A1: Insights into virulence, natural competence and Pasteurellaceae phylogeny. J. Bacteriol. 188: 7257-7266.
Firth, M.A., D.P. Moore, Y. Pei, P.E. Shewen, R.Y.C. Lo, D. Yoo, and D.C. Hodgins. (2006) Cloning of a gene fragment encoding bovine complement component C3d with expression and characterization of derived fusion proteins. Vet. Immuno. Immunopathol. 114: 61-71.
van der Vinne, A.N., R.Y.C. Lo,and P.E. Shewen. (2005) Construction and analysis of a luxS mutant in Mannheimia haemolyticaA1. Vet. Microbiol. 110: 53-60.
Renelli, M., V. Matias, R.Y.C. Lo, and T.J. Beveridge. (2004) Characterization of DNA-containing membrane vesicles of Pseudomonas aeruginosa PAO1 and their genetic transformation potential. Microbiology, 150: 2161-2169.
Ziauddin, A., R.W.H. Lee, R.Y.C. Lo, P.E. Shewen, and J.N. Strommer. (2004) Transformation of alfalfa with a bacterial fusion gene, Mannheimia haemolytica A1 leukotoxin50-gfp: Response with Agrobacterium tumefaciens strains LBA4404 and C58. Plant Cell, Tissue & Organ Culture. 79: 271-278.
Lee, R.W.H., A. N. Pool, A. Ziauddin, R.Y.C. Lo, P.E. Shewen, and J.N. Strommer. (2003) Edible vaccine development: Stability of Mannheimia haemolytica A1 leukotoxin50 during post-harvest processing and storage of field-grown transgenic white clover. Molec. Breeding. 11: 259-266.
Shewen, P.E., C.W. Lee, A. Perets, D.C. Hodgins, K. Baldwin and R.Y.C. Lo. (2003) Efficacy of recombinant sialyglycoprotease in protection of cattle against pneumonic challenge with Mannheimia (Pasteurella) haemolytica A1. Vaccine. 21: 1901-1906.
McNeil, H.J, P.E. Shewen, R.Y.C. Lo, J.A. Conlon, M.W. Miller and I.K. Barker. (2002) Mannheimia haemolytica serotype 1 and Pasteurella trehalosi serotype 10 culture supernatants contain fibrinogen-binding proteins. Vet. Immun. Immunopathol. 90: 107-110.
McKerral, L.J., and R.Y.C. Lo. (2002) Construction and characterization of an acapsular mutant of Mannheimia haemolytica A1. Infect. Immun. 70: 2622-2629.
Malott, R.J., and R.Y.C. Lo. (2002) Studies on the production of quorum sensing signal molecules in Mannheimia haemolytica A1 and other Pasteurellaceae species. FEMS Microbiol. Letts. 206: 25-30.
Graham, M.R, and R.Y.C. Lo. (2002) A putative iron regulated TonB-dependent receptor of Mannheimia (Pasteurella) haemolytica A1 that undergoes phase variation. Vet. Microbiol. 84: 53-67.
Lee, R.W.H., J.N. Strommer, D. Hodgins, P.E. Shewen, Y. Niu and R.Y.C. Lo. (2001) Towards development of an edible vaccine against bovine pneumonic pasteurellosis using transgenic white clover expressing a Mannheimia haemolytica A1 Lkt50 fusion protein. Infect. Immun. 69: 5786-5793.
Lo, R.Y.C., L.J. McKerral, T.L. Hills, and M. Kostrzynska. (2001) Analysis of the capsule biosynthetic locus of Mannheimia (Pasteurella) haemolytica A1 and proposal of a nomenclature system. Infect. Immun. 69: 4458-4464.