John Parkinson

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 Biochemistry 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.

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. For example, we recently published the first genome scale metabolic reconstruction for Toxoplasma gondii in which we used constraints based modelling to reveal strain specific differences in metabolic potential. Our study results support a novel evolutionary strategy, in which changes in the expression of enzymes associated with 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 systems biology framework that allows taxa to be linked to specific functions.

Courses Taught

BCH2131H Genomics of Infectious Diseases
BCH428H Genomics of microbial communities in human health and beyond
BCH374Y1 Research Project in Biochemistry
BCH473Y Advanced Research Project in Biochemistry

Awards and Distinctions

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