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.

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.

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).

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