John Parkinson , PhD
Molecular Structure & Function
University of Toronto
Biochemistry & Molecular and Medical Genetics
Dr. John Parkinson graduated from the University of Bath with a bachelor of science in Applied Biology in 1990. After receiving a PhD in Biochemistry from the University of Manchester in 1995, Dr. Parkinson completed a NATO fellowship at the University of Manitoba. From 1997 to 2000, Dr. Parkinson was awarded a fellowship at the Edinburgh Centre for Protein Technology, University of Edinburgh and from 2000 to 2003 completed another fellowship at the University of Edinburgh on Nematode genomics. In 2003 Dr. Parkinson joined the Research Institute at The Hospital for Sick Children.
- Evolution of biological complexity
- Parasites and bacterial pathogens
- Computational systems biology
The application of various 'omic'-technologies has lead to the generation of vast amounts of data detailing not only the thousands of genes that make up an individual, but also how these genes are organized and operate, paving the way for an exciting new era of 'systems biology'.
Research in the Parkinson lab is focused on applying computational tools to study the evolution and operation of biological systems, and how changes in these systems can lead to human disease. Specific systems of interests range from those implicated in infectious disease to those that can modify our risk to cardiovascular disease.
Specific areas of research:
Identification of novel anti-parasitic therapeutics
Toxoplasma gondii is a singled celled eukaryotic parasite related to Plasmodium, responsible for toxoplasmosis. Toxoplasma infects one in five people in Canada. Initial infection typically causes flu-like symptoms in adults before it resolves into a life-long, chronic infection. However, it is also known to cause serious ocular disease in healthy adults, is a leading cause of foodborne illness in North America, and can cause life-threatening disease in pregnant women, transplant patients, and the immunocompromised. Despite its importance relatively few effective treatments are available. Furthermore, with the emergence of new strains resistant to available prophylactics, new classes of anti parasitic are urgently required. Applying comparative genomics and mathematical models the Parkinson lab identifies and characterizes the genetic innovations associated with the parasite that allows it to survive and persist within its host. Central to this goal, researchers in the lab have recently reconstructed a working model of the parasites metabolism that allows the generation of hypotheses concerning its role in maintaining infection. Through collaborations at the University of Toronto and the NIH, these hypotheses are tested and refined through the use of established in vitro and in vivo models. Through these studies, the Parkinson lab aims to identify critical enzymes that attenuate parasite virulence and may therefore represent useful therapeutic targets.
Mapping and analysis of protein interaction networks
In another research strand, through collaborations with other researchers here in Toronto, the Parkinson lab is involved in constructing and analysing high quality ‘road maps’ that detail how bacterial proteins are organized into higher level systems such as protein complexes and signaling pathways. In addition to providing unprecedented insights into the structure and organization of these systems, these road maps provide valuable scaffolds on which other types of data may be integrated. For example, in separate projects related to cystic fibrosis and type 1 diabetes, the lab is currently exploring the use of these scaffolds for interpreting metatranscriptomic datasets to gain molecular level insights into the dynamics of microbial communities in the lung and gut.
The extracellular matrix
The extracellular matrix (ECM) provides multicellular organisms with their basic biological form. The Parkinson lab is particularly interested in the impact of genetic variations on the organization and operation of the extracellular matrix. Due to their important structural role in the aorta, defects in the components of elastic fibres have been implicated in heart disease. In initial studies of the core component of these fibres - elastin - the Parkinson lab has identified a series of polymorphisms in the human population, that through biochemical reconstructions, have been shown to impact its function. Employing 'next generation' sequencing technology, the lab aims to identify additional sequence variants that may predispose an individual to late onset cardiovascular disease.
- Canadian Institutes of Health Research
- Heart and Stroke Foundation of Ontario
- Natural Sciences and Engineering Research Council of Canada
- Juvenile Diabetes Research Foundation
- NATO Post-Doctoral Fellowship - 1995
- CIHR New Investigator - 2006-2011
- Ontario Ministry of Research and Innovation Early Researcher Award - 2007-2012
Hung, S. and Parkinson, J. (2011) Post-genomics Resources and Tools for Studying Apicomplexan Metabolism. Trends in Parasitology. 27(3):131-40.
Xiong, X., Song, H., On, T., Lochovsky, L., Provart, N. and Parkinson, J. (2011) Phylopro: A web based tool for the generation and visualization of phylogenetic profiles across Eukarya. Bioinformatics. 27(6):877-8
Kahr, W.H.A., Hinckley, J., Li, L., Schwertz, H., Christensen, H., Rowley, J.W., Pluthero, F.G., Urban, D., Fabbro, S., Nixon, B., Gadzinski, R., Storck, M., Wang, K., Ryu, G-Y., Jobe, S.M., Schutte, B.C., Moseley, J., Loughran, N.B., Parkinson, J., Weyrich, A.S., Di Paola, J. (2011) Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome. Nature Genetics. 43(8): 738-40.
Hung, S., Wasmuth, J., Sanford, C. and Parkinson, J. (2010) DETECT - A Density Estimation Tool for Enzyme ClassificaTion and its application to Plasmodium falciparum. Bioinformatics. 26: 1690-1698
On, T., Xiong, X., Pu, S., Turinsky, A., Gong, Y., Emili, A., Zhang, Z., Greenblatt, J., Wodak, SJ. and Parkinson, J. (2010) The evolutionary landscape of the chromatin modification machinery. Proteins. 78:2075-2089
Peregrin-Alvarez, J.M., Xiong, X., Su, C. and Parkinson, J. (2009) The modular organization of protein interactions in Escherichia coli. PLoS Computational Biol. 5(10): e1000523.
Peregrin-Alvarez, J.M., Sanford, C and Parkinson, J. (2009) The conservation and evolutionary modularity of metabolism. Genome Biology. 10:R63
Wasmuth, J., Daub, J., Peregrin-Alvarez, J.M., Finney, C.A.M. and Parkinson, J. (2009) The origins of apicomplexan sequence innovation. Genome Research. 19:1202-1213.
He, D. and Parkinson, J. (2008) SubSeqer: A graph-based approach for the detection and identification of repetitive elements in low-complexity sequences. Bioinformatics. 24: 1016-17.
Su, C., Peregrin-Alvarez, J.M., Butland, G., Phanse, S., Fong, V., Emili, A. and Parkinson, J. (2008) Bacteriome.org – An integrated protein interaction database for E. coli. Nucleic Acids Research. 36: D632-36.
Peregrin-Alvarez, J.M. and Parkinson, J. (2007) The Global Landscape of Sequence Diversity. Genome Biology. 8:R238
Ghedin, E., Wang, S., Spiro, D., Caler, E., Zhao, Q., Crabtree, J., Allen, J.E., Delcher, A.L., Guiliano, D.B., Miranda-Saavedra, D., Angiuoli, S.V., Creasy, T., Amedeo, P., Haas, B., El-Sayed, N.M., Wortman, J.R., Feldblyum, T., Tallon, L., Schatz, M., Shumway, M., Koo, H., Salzberg, S.L., Schobel, S., Pertea, M., Pop, M., White, O., Barton, G.J., Carlow, C.K.S., Crawford, M.J., Daub, J., Dimmic, M.W., Estes, C.F., Foster, J.M., Ganatra, M., Gregory, W.F., Johnson, N.M., Jin, J., Komuniecki, R., Korf, I., Kumar, S., Laney, S., Li, B-W., Li, W., Lindblom, T.H., Lustigman, S., Ma, D., Maina, C., Martin, D., McCarter, J.P., McReynolds, L., Mitreva, M., Nutman, T.B., Parkinson, J., Peregrín-Alvarez, J.M., Poole, C., Ren, Q., Saunders, L., Sluder, A.E., Smith, K., Stanke, M., Unnasch, T.R., Ware, J., Wei, A.D., Weil, G., Williams, D.J., Zhang, Y., Williams, S.A., Fraser-Liggett, C., Slatko, B., Blaxter, M.L. and Scott, A.L. (2007) Draft genome of the filarial nematode parasite Brugia malayi. Science. 317(5845):1756-60.
Krogan N.J., Cagney G., Yu H., Zhong G., Guo X., Ignatchenko A., Li J., Pu S., Datta N., Tikuisis A.P., Punna T., Peregrin-Alvarez J.M., Shales M., Zhang X., Davey M., Robinson M.D., Paccanaro A., Bray J.E., Sheung A., Beattie B., Richards D.P., Canadien V., Lalev A., Mena F., Wong P., Starostine A., Canete M.M., Vlasblom J., Wu S., Orsi C., Collins S.R., Chandran S., Haw R., Rilstone J.J., Gandi K., Thompson N.J., Musso G., St Onge P., Ghanny S., Lam M.H., Butland G., Altaf-Ul A.M., Kanaya S., Shilatifard A., O'shea E., Weissman J.S., Ingles C.J., Hughes T.R., Parkinson J., Gerstein M., Wodak S.J., Emili A., Greenblatt J.F. (2006) Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. Nature. 440, 637-643.
Butland, G., Peregrin-Alvarez, J.M., Li, J., Yang, W., Yang, X., Canadien, V., Starostine, A., Richards, D., Beattie, B., Krogan, N., Davey, M., Parkinson, J., Greenblatt, J., Emili, A. (2005) Interaction Network Containing Conserved and Essential Protein Complexes in Escherichia coli. Nature. 433, 531-537.
Parkinson, J., Mitreva, M., Whitton, C., Thomson, M., Daub, J., Martin, J., Schmid, R., Hall, N., Barrell, B., Waterston, R.H., McCarter, J.P., Blaxter, M.L., (2004) A transcriptomic analysis of the phylum Nematoda. Nature Genetics. 36, 1259-1267.
Peregrin-Alvarez, J., Yam, A., Sivakumar, G., Parkinson, J. (2005) PartiGeneDB - Collating partial genomes. Nucleic Acids Research. 33, D303-307
Parkinson, J., Mitreva, M., Whitton, C., Thomson, M., Daub, J., Martin, J., Schmid, R., Hall, N., Barrell, B., Waterston, R.H., McCarter, J.P., Blaxter, M.L., (2004) A transcriptomic analysis of the phylum Nematoda. Nature Genetics. 36, 1259-1267..