Brian Dixon

Bachelor of Science (BSc) Wilfrid Laurier University (WLU), Master of Science (MSc) Guelph, Doctor of Philosophy (PhD) Dalhousie

Email: bdixon@uwaterloo.ca

Telephone: (519) 888-4567 ext. 32665

Office: Biology 1 276

Research interests

Research in my laboratory is directed towards characterizing fish immune systems at the molecular level. A detailed knowledge of the molecules used as signals and receptors in the mammalian immune system has allowed more effective control of disease through vaccines and drugs. However, only a handful of immunologically important molecules have been isolated from fish, despite the growing need for vaccines and drugs to control diseases in aquaculture. A deeper knowledge of the molecules involved in teleost immune systems also provides insight into the evolution and function of equivalent molecules in mammalian immune systems.

To date my research program has focused on the Major Histocompatibility Complex (MHC) receptors. These molecules are present on the surface of every cell in the body of vertebrates and are the key molecules which decide what belongs to the body and what is a pathogen. I was the first researcher to isolate an expressed MHC gene from fish, and produced the antibodies that allowed the first demonstration that they are present on the surface of fish cells. MHC receptors are highly polymophic and I have performed experiments to measure the evolution of MHC polymorphism in a fish population.

One current research project in my laboratory focuses on fish lymphokines. Lymphokines are small messenger molecules that are secreted by immune system cells in order to pass signals to other cells. I was the first researcher to isolate a gene from rainbow trout that encodes a chemokine (CK-1). Chemokines attract lymphocytes to sites of injury and then activate them. We are using this gene to make recombinant trout chemokine in bacteria and cultured fish cells. The recombinant protein will be used in functional assays and also to make antibodies that will help to elucidate its function. A detailed knowledge of the function of this molecule will enable the design of improved vaccines for aquaculture. We have also isolated two other trout chemokines; CK-2, isolated in collaboration with Dr. Roy Sundick of Wayne State University School of Medicine and CK2.1 a related molecule. These are both CC chemokines with mucin stalks that are characteristic of CXXXC or CXC chemokines in mammals and we are also currently producing recombinant proteins for use in functional studies. This project is funded by NSERC.

The second ongoing research project is an examination of the effects of toxic chemicals on the immune systems of Leopard Frogs. Amphibians world-wide are disappearing and one possible cause is that environmental toxins are suppressing their immune systems, causing them to succumb to diseases that they could ordinarily survive. We have shown that small doses of pesticides – 1 part per million down to 50 parts per billion – can reduce antibody responses to 1% of control levels. In the next stage of this project, laboratory frogs have been fed worms contaminated with various toxins and have shown similar effects. We hope to continue this work by doing skin exposure tests and examining other toxins effects. This work is a collaboration with Dr. Doug Haffner of the Great Lakes Institute for Environmental Research in Windsor and Point Pelee National Park. This project is funded by the Toxic Substances Research Initiative.

A third research project we are just initiating will use MHC polymorphism to determine the population structure of Walleye and Yellow Perch in the western basin of Lake Erie. The Walleye in the basin spawn in several different locations, notably shallows in the middle of the lake and inflowing rivers. The contribution of each of these groups to the lake fisheries in unclear. We hope to determine if these groups of fish are different populations or if they are in fact a single population. Fish sampled from Lake St Clair and the Bay of Quinte in Eastern Lake Ontario will be used as examples of a different population. Yellow Perch, which are thought to be composed of a single population will also be typed as a control group. This project is a collaboration with Dr's Peter Sale and Brian Fryer from the Great Lakes Institute of Environmental Research at the University of Windsor and Dr Tim Johnson from the Ontario Ministry of Natural Resources. The project is funded by NSERC.

The fourth area of research in my laboratory is examining temperature dependent regulation of MHC proteins in Salmonids. Carp turn off the expression of their MHC class 1 receptors at low temperatures, rendering them potentially vulnerable to viral infections. Many of the diseases afflicting salmonids in aquaculture are caused by pathogens that live in the water all summer, but only become pathogenic in the fall when the water temperature drops. We are investigating the possibility that the salmonid diseases break out because they are also turning off MHC gene expression. If there is a link, we hope to make a transgenic fish that expresses MHC genes at low temperatures that could potentially be more disease resistant. Our initial studies indicate that Salmon do turn off this gene, or at least reduce its expression at low temperatures. This work is a collaboration with Dr Patrick Woo of the University of Guelph and A/F Protein Canada, a Newfoundland fish biotechnology company. This project is funded by NSERC and through the AquaNet Network Centres of Excellence.

Selected publications

• Gantner, K., Michaud, W.K., Veillette, J., Bajno, R., Muir, D.C., Vincent, W., Dixon B., Power, M., Reist, J.D., Pienitz, R. and Hausmann, S. Arctic char (Salvelinus alpinus) in Pingualuk Lake (Nunavik, Canada): genetics, trophic ecology, and contaminat analysis. Arctic (Accepted Oct. 2011).
• Conejeros P, Power M, Alekseyev S, Dixon B. Global MH Class II (Beta) polymorphism in Arctic charr (Salvelinus alpinus L.) Journal of Fish Biology (Accepted Nov 2011) MS 11-033.
• Kawano A, Dixon B, Bols N. and Lee L.E.J. Establishment of a myofibroblast cell line from the gastrointestinal tract of Atlantic salmon, Salmo salar MDIBL Bulletin 49: 87-90, 2010.
• Stet, R.J.M., Kruiswijk, C.P., and Dixon, B. Major histocompatibility lineages and immune gene function in teleostean fishes: The road less taken. Invited Review. Critical Reviews in Immunology. In Press (2003).
• Lally, J., Al Anouti, F., Bols, N.C. and Dixon, B. Functional characterization of CK-1, a putative chemokine from rainbow trout (Oncorhynchus mykiss). Fish and Shellfish Immunology 15(5): 411-424 (2003).
• Gilbertson, M.K., Haffner, G.D., Drouillard, K., Albert, A. and Dixon, B. Immunosuppression in the Northern leopard frog (Rana pipiens) induced by pesticide exposure. Envir. Tox. Chem 22(1):101-110 (2003).
• Fujiki, K., Smith, C. M., Lei, L., Sundick, R. S. and Dixon, B. Alternate forms of MHC class II-associated invariant chain are not produced by alternative splicing in rainbow trout (Oncorhynchus mykiss) but are encoded by separate genes. Developmental and Comparative Immunology. . 27(5): 377-391 (2003).
• Fujiki, K., Nakao, M. and Dixon, B. Molecular cloning and characterization of a carp (Cyprinus carpio) cytokine-like cDNA that shares sequence similarity with IL-6 subfamily cytokines. Developmental and Comparative Immunology. 27(2): 127-136 (2003).
• Fujiki, K., Gauley, J., Bols, N.C. and Dixon, B. Genomic cloning of novel isotypes of rainbow trout interleukin-8. Immunogenetics. 55(2): 126-131 (2003).
• Fujiki, K. Gerwick, L., Bayne, C.J., Mitchell, L., Gauley, J., Bols, N. and Dixon, B. Molecular cloning and characterization of rainbow trout (Oncorhynchus mykiss) CCAAT/enhancer binding protein b. Immunogenetics. 55(4): 253-261 (2003).
• Fujiki, K., Gauley, J., Bols, N. and Dixon, B. Cloning and characterization of cDNA clones encoding CD9 from Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). Immunogenetics. 54: 604-609 (2002).
• Lei, L., Fujiki, K., Dixon, B. and Sundick R. S. Cloning of CK2, a CC chemokine with a CXXXC type structure from rainbow trout (Oncorhynchus mykiss). Cytokine. 17(2): 71-81 (2002).
• Shand R. and Dixon B. Teleost Major Histocompatibility Genes: Diverse but not Complex. Invited Review. Mod Asp Immunobiol. 2(2): 66-72 (2001).
• Fujiki, K., Booman M., Chin-Dixon E. and Dixon, B. Cloning and characterization of cDNA clones encoding membrane bound and potentially secreted major histocompatibility class I receptors from Walleye (Stizostedion vitreum). Immunogenetics. 53:760-769 (2001).
• Dixon, B. and Stet R.J.M. The relationship between major histocompatibility receptors and innate immunity in teleost fish. Invited Review. Develop. Comp. Immunol. 25(8-9): 683-699 (2001).
• Dixon, B., B.P.S. Shum, E.J. Adams, K.E. Magor, R.P. Hedrick, D.G. Muir and P. Parham. 1998. CK-1, a putative chemokine of rainbow trout (Oncorhynchus mykiss). Immunological Reviews. 166: 345-352.
• Rodrigues, P.N.S., Dixon, B., Roelofs, J., Rombout, J.H.W.M., Egberts, E., Pohajdak, B. and Stet, R.J.M. Expression and temperature dependent regulation of the beta2-microglobulin (Cyca-B2m) gene in a cold-blooded vertebrate, the common carp (Cyprinus carpio L.). Developmental Immunology 5(4): 263-275 (1998).
• Dixon, B., Nagelkerke, L.A.J., Egberts, E. and Stet, R.J.M. 1996. Evolution of cyprinid major histocompatibility complex class II beta genes as reflected in the large barbels (Barbus Intermedius complex) of Lake Tana. Immunogenetics 44: 419-431.
• Dixon, B., van Erp, S.H.M., Rodrigues, P.N.S., Egberts, E. and Stet, R.J.M. 1995. Fish Major Histocompatibility Complex Genes: An Expansion. Dev. Comp. Immunol. 19: 109-133.
• Dixon, B., Stet, R.J.M., van Erp S.H.M., Pohajdak, B. 1993. Characterisation of beta-2-microglobulin transcripts from two teleost species. Immunogenetics. 38: 27-34.

Potential projects for new students

• Characterization of rainbow trout Major Histocompatibility proteins using polyclonal antibodies.
• Characterization of rainbow trout chemokine expression and function using polyclonal antibodies.
• Characterization of rainbow trout invariant chain expression and function using polyclonal antibodies.
• An examination of the effects of toxins on the anuran immune system.
• Molecular characterisation of Walleye populations using MHC polymorphism.
• Investigation temperature dependent regulation of salmonid MHC expression and its role in salmonid diseases.
• Cloning and characterizing novel fish immune system genes.