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John Dalton

John Dalton

Full Professor

(BSc, PhD Dublin, Ireland )

Office: (514) 398-8668
Fax: (514) 398-7857
john [dot] dalton [at] mcgill [dot] ca (Email)

Research Interests

Publications

Our research interest has always centered on the understanding of the biology and biochemistry of parasitic organisms, and on the interplay between parasites and their hosts. In particular, I am interested in the molecules that parasites release to alter the physiology of their hosts. Of critical importance is how parasites manipulate host immune responses to their advantage. While many aspects of this research are basic, the ultimate goal is the discovery of a strategy(s) by which we can protect animals and humans from parasitic infections by either chemotherapeutic (drugs) or immunological (vaccines) means. Accordingly, we have always been cognizant of the applied and/or commercial potential of the work which has led to a number of patent applications.
 
More specifically, in our research on malaria (Plasmodium sp.) we have identified several aminopeptidase enzymes which the parasites employ to release amino acids from haemoglobin within erythrocytes. The parasites utilize these amino acids for protein anabolism and, hence, as our studies show, blocking of these enzymes with broad-range or specific inhibitors prevent parasite growth. We have recently discovered several lead compounds with in vivo activity against rodent models of malaria that will be used for the future development of novel antimalarials.
 
Research on the Schistosoma sp., the causative agents of schistosomiasis in animals and man (infects >200 million people in >70 countries), and liver fluke disease (Fasciola hepatica; infects mainly domestic aniamls but also humans) has led to the isolation and characterisation of a battery of enzymes that these parasites employ to systematically degrade haemoglobin from host red blood cells which they use as nutrient. Apart from characterizing the physico- and biochemico-properties of these enzymes we have used these as vaccines against these disease. Other molecules, such as the anti-oxidants, peroxiredoxins, are involved in detoxifying ROS derived from parasite metabolism or by attacking immune effector cells. Our recent studies have demonstrated a role for proteases and peroxiredoxin in modulating the host’s innate immune mechanisms.
 
Our area of research also includes the immunology of infectious diseases, the regulation of immune responses by parasites and the cross-regulation of immune response between parasitic infections and concurrent infection with bacterial pathogens such as Bordetella pertussis and Salmonella sp., and protozoans such as Toxoplasma gondii. We also are investigating the activity of parasite molecules on host immune cells (dendritic, macrophages and T cells) and the mechanism by which they may alter their function. These molecules have potential in the therapeutic treatment of inflammatory diseases of humans (e.g. diabetes, rheumatic diseases, IBD, Chrone’s Disease).
The techniques that are used in my laboratory can be divided under several headings including -

  1. Molecular Biology - gene discovery and isolation, cloning and characterisation, general bioinformatics, recombinant expression of cDNAs in prokaryotic (E. coli) yeast (Saccharomyces cerevisiae and Pichia pastoris) and eukaryotic (insect cells) expression systems, optimisation of fermentation processes.
  2. Biochemistry - purification of native and recombinant proteins by conventional chromatographic techniques, protein analysis and proteomics, enzyme substrate and inhibitor analysis.
  3. Immunology - routine ELISA, cell isolation, proliferation assay, signal transduction, and cytokine measurement and analysis by ELISA, FACs analysis and RT-PCR/Real-time RT-PCR.
  4. Proteomics/Bioinformatics - We have employed the Applied Biosciences QSTAR® Elite System, (LC/MS/MS using the Tempo™ nano LC system) to characterize pathogen secreted proteins that influence host immune responses.
  5. General expertise - our general area of expertise is in molecular biology, enzymology, immunodiagnostics, immunology, vaccinology in small and large animals, biochemistry, culturing of protozoan and helminth parasites, and basic cell biology.