John Parkinson

John Parkinson

Professor

BSc, University of Bath, 1990
PhD, University of Manchester, 1995

Address Peter Gilgan Center for Research and Learning
20th Floor, RM 20.9709
686 Bay Street
Toronto, ON M5G 0A4
Lab Parkinson Lab
Lab Phone 416-813-7654 ext. 301846
Office Phone 416-813-5746
Email jparkin@sickkids.ca

Dr John Parkinson is a computational biologist whose research interests focus on the impact of microbiota on human health. After completing his PhD at the University of Manchester, studying molecular self-assembly, John spent a year at the University of Manitoba investigating diatom morphogenesis. In 1997, John moved to Edinburgh where he applied computer models to study the evolution of complement control proteins with Dr Paul Barlow. With the emergence of high throughput sequencing, John then led the bioinformatics efforts associated with the parasitic nematode expressed sequence tag project, responsible for the processing and curation of sequence data from 30 species of parasitic nematodes. John was recruited to the Hospital for Sick Children in 2003 and was promoted to Senior Scientist in 2009. He holds cross-appointments in both the departments of Biochemsitry and Molecular Genetics at the University of Toronto. Current lab interests center on the role of the microbiome in health and disease as well as the mechanisms that allow  pathogens and parasites to survive and persist in their human hosts.  Key to this research is the integration of computational systems biology analyses with comparative genomics to explore the evolution and operation of microbial pathways driving pathogenesis. Findings from our research programs are helping guide new strategies for therapeutic intervention.

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Research Lab

Sarcocystis genome comparison

Genome comparison between Sarcocystis neurona and Toxoplasma gondii

Research in the Parkinson lab is largely driven through the development and application of computational methods.We work with an extensive network of clinicians, parasitologists and immunologists to generate and analyse genomic, metagenomic, metatranscriptomic and metabolomic datasets from a variety of patient and environmental samples. Exploiting the University of Toronto’s high performance computing platform (SciNet), these datasets are integrated to develop new insights into the evolution of parasites, pathogens and microbiomes and how their interact with their host. Trainees in our lab typically possess expertise in programming (C++/Java/Perl / Python); cloud computing; relational database management; maths and statistics. Over the course of their studies, trainees typically acquire skills in machine learning algorithms; genome annotation; next generation sequencing; metagenomics; phylogenetics; sequence processing; network biology; metabolic reconstruction; and constraints based modelling.

In addition to our dry lab activities, we also maintain a wet lab with tissue culture facilities for the culturing of  Toxoplasma strains for biochemical and proteomic investigations. Below is an image of a GFP-tagged strain of parasites growing in HFF cells.

Toxo_in_Cells

Learn more: Parkinson Lab

Research Description

Parasites and Microbes in Health and Disease

To survive and persist within their human hosts, infectious disease agents such as bacterial pathogens and parasites have acquired a vast battery of molecular innovations. With the recent availability of genomics and proteomics resources for many of these organisms, the challenge is to identify pathogen-related processes that mediate the most critical roles. The Parkinson lab seeks to exploit these datasets through the integration of computational systems biology analyses with comparative genomics to explore the organization and operation of these processes. Capitalizing on recent developments in the analysis of complex microbial communities, we are also investigating how the composition and function of the gut microbiome modifies the ability of pathogens and parasites to cause disease. Ultimately our aim is to identify pathways, encoded by the parasite, the host, or even the host microbiome, that can be targeted for therapeutic intervention.

Parasite Innovations

The increasing prevalence of infections involving intracellular apicomplexan parasites such as Plasmodium, Toxoplasma, and Cryptosporidium (the causative agents of malaria, toxoplasmosis and cryptosporidiosis respectively) represent significant global healthcare burdens. Despite their significance, few treatments are available; a situation that is likely to deteriorate with the emergence of new resistant strains of parasites. To help drive drug development programs, sequencing initiatives have resulted in the generation of many apicomplexan genomes. Comparisons between these genomes are beginning to identify both conserved processes mediating fundamental roles in parasite survival and persistence, as well as lineage specific-adaptations associated with divergent life-cycle strategies.

Toxo_Metabolism1

For example, we recently published the first genome scale metabolic reconstruction for Toxoplasma gondii (Song et al 2013,  above). in which we used constraints based modelling to reveal strain specific differences in metabolic potential. Our study support a novel evolutionary strategy, in which changes in the expression of enzymes associated withe energy production allows the parasite to extend its host range.

Functional Interrogation Of Microbiomes Through Metatranscriptomics

Bacteria do not live in isolation but tend to form parts of communities or ‘microbiomes’, displaying complex inter-dependencies between themselves and their environment. Recent advances in high-throughput sequencing are driving new programs of research that are profoundly transforming our understanding of the relationships between microbiomes and their environments. My lab is pioneering the use of whole-microbiome gene expression profiling (‘meta-transcriptomics’) as a means of gaining functional insights into the organization and operation of complex microbial communities. Working with clinicians, we sequence and analyse samples from patients with Cystic fibrosis, Diabetes, Inflammatory Bowel Disease and Obesity. Key to these studies is the ability the use of a systemsbiology framework that allows taxa to be linked to specific functions.

Transporters_microbiome

The figure above shows the contribution of bacterial taxa to transporter functions. Each pie chart represents a transporter protein, with segments indicating species abundance for that protein. Top panel – mouse gut; bottom panel – kimchi. Note in the mouse gut sample that many transporter functions are represented by bacteriodetes (green) and protobacteria (blue). In the kimchi sample, proteins involved in oligopeptide transport are well expressed, largely encoded by Lactobacillus (purple) and Weissella (red).

Awards & Distinctions

2006-2011 — CIHR New Investigator
2007-2012 — Ministry of Research and Innovation - Early Researchers Award
1995-1996 — NATO Postdoctoral Fellowship
1991-1995 — Wellcome Trust Mathematical Biology Fellowship

Courses Taught

BCH428H Genomics of microbial communities in human health and beyond
BCH473Y Advanced Research Project in Biochemistry
BCH375H Research Project in Biochemistry
BCH373H Research Project in Biochemistry

Extra-Departmental Courses

MGY1012 Topics in Molecular Genetics

Publications

View all publications on PubMed

Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality
Jiang Y, Xiong X, Danska J, Parkinson J.
Microbiome 2016 4:2  Read

The genome of Onchocerca volvulus, agent of river blindness.
Cotton JA, Bennuru S, Grote A, Harsha B, Tracey A, Beech R, Doyle SR, Dunn M, Hotopp JC, Holroyd N, Kikuchi T, Lambert O, Mhashilkar A, Mutowo P, Nursimulu N, Ribeiro JM, Rogers MB, Stanley E, Swapna LS, Tsai IJ, Unnasch TR, Voronin D, Parkinson J, Nutman TB, Ghedin E, Berriman M, Lustigman S.
Nature Microbiology 2016 2:16216.  Read

Hyperscape: visualization for complex biological networks
Cromar GL, Zhao A, Yang A, Parkinson J.
Bioinformatics 2015 31: 3390-3391  Read

Panorama of ancient metazoan macromolecular complexes.
Wan C, Borgeson B, Phanse S, Tu F, Drew K, Clark G, Xiong X, Kagan O, Kwan J, Bezginov A, Chessman K, Pal S, Cromar G, Papoulas O, Ni Z, Boutz DR, Stoilova S, Havugimana PC, Guo X, Malty RH, Sarov M, Greenblatt J, Babu M, Derry WB, Tillier ER, Wallingford JB, Parkinson J, Marcotte EM, Emili A.
Nature 2015 525:339-344.  Read

New tricks for ‘old’ domains: How novel architectures and promiscuous hubs contributed to the organization and evolution of the ECM
Cromar G, Wong KC, Loughran N, On T, Song H, Xiong X, Zhang Z, Parkinson J.
Genome Biology and Evolution 2014 Oct 15. pii: evu228.  Read

Metabolic reconstruction identifies strain-specific regulation of virulence in Toxoplasma gondii.
Song C, Chiasson MA, Nursimulu N, Hung SS, Wasmuth J, Grigg ME, Parkinson J.
Molecular Systems Biology 2013 9: 708.  Read

The genomes of four tapeworm species reveal adaptations to parasitism.
Tsai IJ, Zarowiecki M, Holroyd N, Garciarrubio A, Sanchez-Flores A, Brooks KL, Tracey A, Bobes RJ, Fragoso G, Sciutto E, Aslett M, Beasley H, Bennett HM, Cai J, Camicia F, Clark R, Cucher M, De Silva N, Day TA, Deplazes P, Estrada K, Fernández C, Holland PW, Hou J, Hu S, Huckvale T, Hung SS, Kamenetzky L, Keane JA, Kiss F, Koziol U, Lambert O, Liu K, Luo X, Luo Y, Macchiaroli N, Nichol S, Paps J, Parkinson J, Pouchkina-Stantcheva N, Riddiford N, Rosenzvit M, Salinas G, Wasmuth JD, Zamanian M, Zheng Y; Taenia solium Genome Consortium., Cai X, Soberón X, Olson PD, Laclette JP, Brehm K, Berriman M.
Nature 2013 496. 57-63.  Read

A transcriptomic analysis of Echinococcus granulosus larval stages: implications for parasite biology and host adaptation.
Parkinson J, Wasmuth JD, Salinas G, Bizarro CV, Sanford C, Berriman M, Ferreira HB, Zaha A, Blaxter ML, Maizels RM, Fernández C.
PLoS Neglected Tropical Diseases 2012 6(11): e1897.  Read

Evolution and architecture of the inner membrane complex in the asexual and sexual stages of the malaria parasite.
Kono M, Herrmann S, Loughran NB, Cabrera A, Engelberg K, Lehmann C, Sinha D, Prinz B, Ruch U, Heussler V, Spielmann T, Parkinson J*, Gilberger TW.*
Molecular Biology and Evolution 2012 29(9):2113-2132.  Read

The origins of apicomplexan sequence innovation.
Wasmuth J, Daub J, Peregrín-Alvarez JM, Finney CA, Parkinson J.
Genome Research 2009 19:1202-1213.  Read