Associate Professor, Department of Biology
PhD, University of Waterloo
Lay Research Summary
Plants produce hundreds of defense compounds essential for their survival. These factors help them respond to environmental cues and fend off pathogens. My lab is focused on understanding the function of a specific group of enzymes called RNA glycosidases. These enzymes damage certain RNAs, inhibit ...read moreing the production of their encoded proteins. RNA glycosidases are not toxic to the plants that make them; however, many have been shown to inhibit the replication of diverse plant and animal viruses. For example, the pokeweed plant produces the ‘pokeweed antiviral protein’, which protects the plant from viral infections. The antiviral protein was also shown to decreases HIV-1 production from infected human immune cells. Therefore, the protective role of this protein in the plant may transcend to human defense as well. Our two main goals are to understand how the enzyme is regulated in plants and to characterize its activity against viruses in human cells. The decline in virus production is largely due to damage of the viral genome, which terminates various steps in the virus lifecycle. We are currently investigating how the antiviral protein specifically targets the virus without being toxic, to develop its potential application as an antiviral agent. read less
Scientific Research Summary
RNA toxins are a group of enzymes that mediate an organism’s response to stress, either by causing apoptosis, regulating growth rate, facilitating a change in development or by directly targeting pathogens. They are nucleases or glycosidases that damage RNA, thereby inhibiting gen ...read moree expression at the translation level. RNA toxins are broadly categorized into four groups, based on their enzyme activity (cleavage of phosphodiester bond or base) and substrates (rRNA, tRNA, or mRNA). The goal of our research is to understand the regulation and develop the application of a glycosidase synthesized by the pokeweed plant, called pokeweed antiviral protein (PAP). Two current research areas: 1) Regulation of the antiviral protein in pokeweed. We have discovered a small negative-strand RNA in pokeweed that binds specifically and cleaves the mRNA of our antiviral protein, reducing its expression. Our preliminary evidence suggests that the small RNA itself is down-regulated by jasmonic acid, which is a plant signaling molecule that controls the expression of several defense genes. Down-regulation of the small RNA would be the first evidence to suggest that our antiviral protein is controlled by the signaling pathway that recognizes virus infection. In addition to the post-transcriptional regulation by the small RNA, we are working to find and sequence the gene’s promoter. We will identify essential elements and determine whether they are controlled by virus infection and/or environmental stress. 2) Potential application of the antiviral protein against HIV-1. By transfecting cell lines with a cDNA encoding the antiviral protein and HIV-1 proviral clone, we have shown that expression of the enzyme decreases viral RNA synthesis, alters its splicing, and reduces HIV-1 protein levels, resulting in substantial decline in virus production. These effects are largely due to depurination of the viral genome by the antiviral protein, which terminates its replication. Our preliminary data also suggest that the antiviral protein improves the natural defense response of cells against HIV-1. We are currently investigating how the antiviral protein specifically targets the virus without being toxic. read less
Centre for Research on Bio-Molecular Interactions (CRBMI)
Pokeweed antiviral protein increases HIV-1 particle infectivity by activating the cellular mitogen activated protein kinase pathway
Journal: PLoS One
Depurination of Brome mosaic virus RNA3 inhibits its packaging into virus particles.
Journal: Nucleic Acids Res.
RNA toxins: mediators of stress adaptation and pathogen defense
Journal: Wiley Interdiscip Rev RNA
Homodimerization of pokeweed antiviral protein as a mechanism to limit depurination of pokeweed ribosomes.
Journal: Mol Plant Pathol.
Suppression of human T-cell leukemia virus I gene expression by pokeweed antiviral protein.
Journal: J Biol Chem.
DNA encoding a plant lipase, transgenic plants, and a method for controlling senescence in plants.
Date Filed: 2004
Number: US# 6774284
Honours & Awards
CFI New Opportunities Award 2002
Premier’s Research Excellence Award 2003
Faculty of Science Excellence in Teaching Award2008
Editorial & Review Boards
Role: #1501 Genes Cells and Molecules
Role: #187 Scholarships and Fellowships
Role: #1501 Genes Cells and Molecules
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