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John Parkinson
Professor
Ph.D., University of Manchester,
UK (1995) |
TMDT Building, East Tower 15th Floor, Rm 15-703
416-813-5746
416 813-7654 x 3016, Admin Assistant: Vaya Apostolopoulos, vaya.apostolopoulos@utoronto.ca
jparkin@sickkids.ca |
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Comparative Genomics and Computational Systems Biology
Lab
Homepage
Research Synopsis
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My labs research is focused on studying the emergence of biological complexity particularly as it pertains to infectious disease. Of particular interest in the human parasite Toxoplasma gondii, a single celled eukaryotic parasite related to Plasmodium, responsible for toxoplasmosis. T. gondii infects one in every 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 and death in North America, and life-threatening disease in pregnant women, transplant patients, and the immunocompromised. Despite its importance relatively few effective treatments are available and with the emergence of new strains resistant to available prophylactics, new classes of anti parasitic are urgently required. Applying comparative genomics and mathematical models we aim to identify and characterize genomic innovations associated with the parasite that allows it to survive and persist within its host. Central to this goal, we have recently reconstructed a working model of the parasites metabolism that allows us to generate hypotheses concerning its role in maintaining infection, as well as identify critical enzymes that attenuate its virulence. Through collaborations at the University of Toronto and the NIH, we are currently performing functional investigations to validate our predictions.
In another research strand, through a collaboration with researchers here in Toronto, we are constructing 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 of these systems, these road maps provide valuable scaffolds on which other types of data may be integrated. For example, we are currently exploring their use for interpreting meta-transcriptomic datasets to gain functional insights into the dynamics of biological systems associated with bacterial communities sampled from the lungs of patients with cystic fibrosis. In a separate project, we are currently integrating comparative genomic data to examine how these networks have evolved.
In a final set of projects, we are examining 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, we have 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, we are currently sequencing the elastin gene from a cohort of individuals diagnosed with aortic aneurysms and dissections, in an attempt to identify additional sequence variants that may predispose an individual to late onset cardiovascular disease.
Selected Publications
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
Hung, S. and Parkinson, J. (2011) Post-genomics Resources and Tools for Studying Apicomplexan Metabolism. Trends in Parasitology. 27(3):131-40.
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.
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