51±¾É«

Current research projects in my lab are focused on:

1. Determining how ammonia and oxygen deprivation alters brain function and metabolism in fishes.
2. Establishing the mode of toxicity of the pesticides, 3-trifluoromethyl-4- nitrophenol (TFM) and niclosamide, which are used to control lamprey populations in the Great Lakes.
3. Describing how gill function and physiological processes in lampreys are altered and controlled as they undergo metamorphosis from filter-feeding, burrow-dwelling larvae to blood-sucking juvenile lamprey that prey on large bodied fishes in the Great Lakes and in the oceans.

Ongoing Projects

(i) Mechanisms of Ammonia Tolerance & Nitrogen Excretion in Fishes.

Ammonia can arise in aquatic environments due to the degradation of organic matter, run-off from agricultural operations or as leachate from landfill sites. In humans, neurotoxic ammonia can build-up in the body due to defects in the liver’s ability to detoxify ammonia arising from protein catabolism. In a collaborative effort with Dr. Les Buck (Department of Zoology, University of Toronto) electrophysiological techniques (Patch Clamp) are being used to establish how ammonia alters the neurophysiology of the brain in fishes subjected to high concentrations of environmental ammonia. In addition to whole animal and neurophysiological studies, Dr. Lucy Lee (WLU, Biology) and I have established cell lines of goldfish brains and other tissues. These cell lines will be used to determine how ammonia affects neuron survival, and to establish the mechanism of ammonia toxicity in brain cells by exposing cells to ammonia in the presence of various drugs that are thought to reduce the ammonia’s toxic effects in the nervous system. These experiments will build upon the findings of recent students who found that the ammonia tolerance of rainbow trout was increased when certain drugs (e.g. MK801, ethanol) were used to reduce nervous system activity. In combination with whole animal studies, cultured brain cells will be useful in vitro models that will be used to ascertain why certain fishes are more tolerant to ammonia than other fishes and mammals.

We are also studying how wastes, such as ammonia urea, are excreted across the gills of primitive fishes such as the lamprey. Using different surgical, pharmacological and molecular approaches a major goal is to determine how the parasitic lampreys rid their bodies of urea and ammonia after ingesting the blood of fishes. Unlike filter feeding larval lampreys, the parasitic lampreys use an oral disc to attach to their hosts, and use their rasping tongue to pierce the hide and then suck the blood from the fish. We recently reported that parasitic lampreys excrete vast quantities of urea after feeding on sharks, which suggest that they have specialized urea transporters for this purpose.

Much of this work is presently being conducted by two undergraduate honours thesis students, but there are opportunities for an M.Sc. student to use cell culture and neurophysiological techniques to learn more about the mechanisms of ammonia toxicity and survival in fishes, or two examine modes of urea excretion in lampreys.

(ii) Mechanisms of Anoxia Tolerance in the Goldfish.

Unlike most vertebrates, in which oxygen starvation can rapidly lead to brain damage or death within minutes, the goldfish readily survives in oxygen depleted environments for days or even weeks. In an ongoing collaboration with Dr. Buck we measured the electrical properties of goldfish brain slices in response to anoxia using whole cell patch clamping. We have observed that the brain of some fish is protected by decreasing the activity of N-methyl-D-aspartate (NMDA) receptors, which are normally involved in processes such as learning and memory, and other ATP consuming enzymes (e.g. Na+/K+ ATPase)

Much of the work so far was completed by honours thesis students, but there are opportunities for an M.Sc. student to use cell culture, immunodetection and neurophysiological studies to learn more about the neurophysiology of domestic and pond-dwelling goldfish during periods of oxygen starvation.

(iii) The Effects of Multiple Metal Interactions and Dissolved Organic Matter on Fish Gill Function.

Although substantial progress has been made in recent years to understand how fish gills respond to metals on an individual basis, rarely are fishes exposed to metals or other toxicants individually. Since most toxicants exist in mixtures, a fundamental goal of my lab is to determine how mixtures of metals alter gill mediated physiological processes such as ion regulation in rainbow trout (Oncorhynchus mykiss). This work uses the Biotic Ligand Model (BLM), which provides details about each metal’s gill binding affinity, to predict how metals such as Cd, Pb and Zn interact with the gill. To test predictions using the BLM, fish survival and gill metal accumulation on the gill are then measured. Gill mediated physiological processes such as ion (Na+, Cl-, Ca2+) uptake are also measured to determine if the physiological responses of fishes can be predicted by the BLM. Dissolved organic matter (DOM) reduces gill metal binding, but different metals have different binding affinities for this ligand. Thus, a longer term goal is determine how the presence of DOM influences fish survival and gill function in fishes exposed to different combinations of metals.

We presently have two M.Sc. students and a Postdoctoral Fellow doing work in this area, but there are opportunities for undergraduate projects.

(iv) Modes of Lampricide Toxicity in Larval Sea Lampreys and Non-target Fishes

This work, funded by the Great Lakes Fishery Commission, is investigating how the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) exerts its toxic effects in fishes. This pesticide is added to streams containing larval sea lampreys as a means to control populations of this invasive species which have plagued fisheries in the Great Lakes. We will use a combination of sub-cellular mitochondrial isolation techniques and whole animal studies to test two hypotheses of TFM toxicity. Using whole body, biochemical and sub-cellular (mitochondrial isolation) techniques, we are testing the hypothesis that TFM interferes with oxidative ATP production, and therefore leads to death in larval lampreys and non-target fishes by causing metabolic arrest. We are collaborating with Dr. Grant McClelland (Department of Biology, McMaster University) and Dr. Yuxiang Wang (Department of Biology, Queen’s University) on this project. A second hypothesis we are testing is that TFM targets the gills of fishes, leading to disturbances to internal ion and water balance that eventually cause collapse of the circulatory system. As our understanding of the mode of TFM toxicity is improved, we hope it will contribute to achieving overall reductions in TFM use, so that TFM treatments can safely continue in the Great Lakes.

We presently have one M.Sc. student working on the physiological effects that TFM has on trout and larval lamprey physiology. There is an opportunity for another M.Sc. student, however, to conduct studies on the routes and mechanisms of TFM entry into fishes in order to further refine TFM application techniques.

(v) Use of Passive Integrated Transponder (PIT) Tags to Monitor the Movements of Brown Trout in the Grand River Tailwater.

In a collaborative effort with the Friends of the Grand River (FOGR), Grand River Conservation Authority, and the Ontario Ministry of Natural Resources (OMNR), the long-term goal of this work is to use surgically implanted passive integrated transponder (PIT) tags to determine if habitat improvement measures (e.g. placement of large cover) are being used by brown trout (Salmo trutta) in the Grand River Tailwater. Another important goal is to use this technique to determine how/if brown trout survival over the winter is affected by limited habitat availability and ice formation. It is suspected that poor over-winter survival is one factor that makes it necessary to annually stock brown trout into the Grand River Tailwater to sustain this internationally recognized fly fishery. This pilot study is designed to assess the feasibility of using a portable PIT tag detector unit to locate fish in the Grand River, and to evaluate the effects that the PIT-tagging procedure has on the short- and long-term health of the trout. Studies are therefore conducted in the field and the laboratory.

There may be an opportunity for further field and laboratory work on PIT tagging in trout by an undergraduate student.

Chapters in Books

Zydlewski, J. and M.P. Wilkie. 2013. Freshwater to seawater transitions in migratory fishes. Chapter 6. Pages 253-326 in Fish Physiology, Volume 32, Euryhaline Fishes.

S.D. McCormick, A.P. Farrell; C.J. Brauner (volume editors), Academic Press. Wilkie, M.P. 2011a. The physiology of lampreys I: Energetics and development. Chapter 252 in The Encyclopedia of Fish Physiology: From Genome to Environment.

A.P. Farrell (editor-in-chief), Elsevier Inc. Wilkie, M.P. 2011b. The physiology of lampreys II: Environmental physiology. Chapter 279 in The Encyclopedia of Fish Physiology: From Genome to Environment.

A.P. Farrell (editor-in-chief), Elsevier Inc.

Papers in Refereed Journals

Clifford, A.M., A.M. Weinrauch, S.L. Edwards, M.P. Wilkie, and G.G. Goss. Flexible ammonia handling strategies using the skin and gill contribute to the high ammonia tolerance of the Pacific hagfish. Am. J. Physiology. In Press.

Dunlop, E. et al. 2017. Rapid evolution meets invasive species control: the potential for pesticide resistance in sea lamprey. Can. J. Fish. Aquat. Sci. In Press.

Wilkie, M.P., A.M. Clifford, S.L. Edwards, and G.G. Goss. 2017. Wide scope for nitrogen catabolism in the foraging Pacific hagfish. Marine Biology. In Press.

Hossein-Javaheri, N. M.P. Wilkie, W.E. Lado, and L.T. Buck. 2017. Stellate and pyramidal neurons in goldfish telencephalon respond differently to anoxia and GABA receptor inhibition. Journal of Experimental Biology. In Press. doi: 10.1242/jeb.146605.

Hlina, B.L., L.R. Tessier, and M.P. Wilkie. 2017. Effects of water pH on the uptake & elimination of a piscicide, 3-trifluoromethyl-4-nitrophenol (TFM), by larval sea lampreys. To be submitted to Comp. Biochem. Physiol. Part C. 200: 9-16. dx.doi.org/10.1016/j.cbpc.2017.05.005

Blair, S.D., M.P. Wilkie, and S.L. Edwards. 2017. Rh glycoprotein immunoreactivity in the skin and its role in extrabranchial ammonia excretion by the sea lamprey (Petromyzon marinus) in fresh water. Canadian Journal of Zoology. Can. J. Zool. 95: 95–105. dx.doi.org/10.1139/cjz-2016-0120.

Lisser, D.F.J, Z.M. Lister, P.Q.H. Pham-Ho, G.R. Scott, and M.P. Wilkie. 2017. Relationship between oxidative stress and brain swelling in goldfish (Carassius auratus) exposed to high environmental ammonia. American Journal of Physiology Regulatory and Integrative Comparative Physiology 312: R114–R124, 201. DOI: 10.1152/ajpregu.00208.2016.

Clemow, Y.H., and M.P. Wilkie. 2015. Effects of Pb plus Cd mixtures on toxicity, and internal electrolyte and osmotic balance in the rainbow trout (Oncorhynchus mykiss). Aquatic Toxicology 161: 76-84.

Henry, M., O. Birceanu, G.B. McClelland, A.M. Clifford, Y.S. Wang, and M.P. Wilkie. 2015. Life-stage dependent responses to the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) provide insight into glucose homeostasis and metabolism in the sea lamprey (Petromyzon marinus). Comparative Biochemistry and Physiology, Part C: Toxicology and Pharmacology 169: 35-45.

Clifford, A.M, G.G. Goss, and M.P. Wilkie. 2015. Adaptations of a deep sea scavenger: Extreme ammonia tolerance and active NH4+ excretion by the Pacific hagfish (Eptatretus stoutii). Comparative Biochemistry and Physiology, Part A: Molecular and Integrative Physiology 182: 64-74.

Wilkie, M.P., J.A.W. Stecyk, C.S. Couturier, S. Sidhu, G.K. Sandvik, and G.E. Nilsson. 2015. Reversible brain swelling in crucian carp (Carassius carassius) and goldfish (Carassius auratus) in response to high external ammonia and anoxia. Comparative Biochemistry and Physiology, Part A: Molecular and Integrative Physiology 184: 65-75.

Birceanu O., L.A. Sorensen, M. Henry, G.B. McClelland, Y.S. Wang and M.P. Wilkie. 2014. The effects of the lampricide 3-trifluoromethy1-4-nitrophenol (TFM) on fuel stores and ion balance in a non-target fish, the rainbow trout (Oncorhynchus mykiss). Comparative Biochemistry and Physiology C- Toxicology and Pharmacology 160: 30-41.

Havixbeck J.J., A.M. Rieger, M.E. Wong, M.P. Wilkie, and D.R. Barreda. 2014. Evolutionary conservation of divergent pro-inflammatory and homeostatic responses in lamprey phagocytes. PLOS ONE, 9(1), e86255.

Binder T.R., D.G. McDonald, and M.P. Wilkie. 2013. Reduced dermal photosensitivity in juvenile sea lampreys (Petromyzon marinus) reflects life-history-dependent changes in habitat and behaviour. Canadian Journal of Zoology 91: 635-639.

Clifford, A.M., M. Henry, A. Smits, D.G. McDonald, R. Bergstedt, and M.P. Wilkie. 2012. Recovery of larval sea lampreys from short-term exposure to the pesticide, 3-Trifluoromethyl-4-nitrophenol (TFM): Implications for sea lamprey control in the Great Lakes. Transactions of the American Fisheries Society 141: 1697-1710.

Winter, A.R., R.C. Playle, D.G. Dixon, U. Borgmann, and M.P. Wilkie. 2012. Interactions of Pb and Cd mixtures in the presence or absence of natural organic matter with the fish gill. Ecotoxicology and Environmental Safety 83: 16-24.

Wilkie, M.P., M. Pamenter, S. Duquette, H. Dhiyebi, G. Skelton, N. Sangha, and L.T. Buck. 2011. The relationship between NMDA receptor function and the high ammonia tolerance of anoxia-tolerant goldfish (Carassius auratus). Journal of Experimental Biology 214: 4107-4120.

Birceanu, O., G.B. McClelland, Y.S. Wang, J.C.L. Brown, and M.P. Wilkie. 2011. The lampricide 3-trifluoromethyl-4-nitrophenol (TFM) uncouples mitochondrial oxidative phosphorylation in both sea lamprey (Petromyzon marinus) and TFM-tolerant rainbow trout (Oncorhynchus mykiss). Comparative Biochemistry and Physiology Part C: 153: 342-349.

Gheorghiu, C., D.S. Smith, H.A. Al-Reasi, J.C. McGeer, and M.P. Wilkie. 2010. Influence of natural organic matter (NOM) quality on Cu-gill binding in the rainbow trout (Oncorhynchus mykiss). Aquatic Toxicology 97: 343–352.

Gillis, P.L, J.C. McGeer, G.L. Mackie, M.P. Wilkie, and J.D.Ackerman. 2010. The effect of natural dissolved organic carbon on the sensitivity of larval freshwater mussels (glochidia) to acute copper exposure. Environmental Toxicology and Chemistry 29: 2519–2528.

Gheorghiu, C., J. Hanna, J.W. Smith, D. S. Smith, and M.P. Wilkie. 2010. Encapsulation and migration of PIT tags implanted in brown trout (Salmo trutta L.). Aquaculture 298: 350-353.

Birceanu, O., G.B. McClelland, Y.S. Wang, and M.P. Wilkie. 2009. The mechanism of lampricide, 3-trifluoromethyl-4-nitrophenol (TFM), toxicity in larval sea lampreys (Petromyzon marinus): A failure of ATP supply to match ATP demand. Aquatic Toxicology 94: 265-274.

Newby, N.C., M.P. Wilkie, and E.D. Stevens. 2009. Morphine uptake, disposition, and analgesic efficacy in the common goldfish (Carassius auratus). Canadian Journal of Zoology 87:388-399.

Weihrauch, D., M.P. Wilkie, and P.J. Walsh. 2009. Ammonia and urea transporters in gills of fish and aquatic crustaceans. Journal of Experimental Biology 212: 1716-1730.

Birceanu, O., M.J. Chowdhury, P.L. Gillis, J.C. McGeer, C.M. Wood, and M.P. Wilkie. 2008. Modes of metal toxicity and impaired branchial ionoregulation in rainbow trout exposed to mixtures of Pb and Cd in soft water. Aquatic Toxicology 89:221-231.

Wilkie, M.P., M.E., Pamenter, S. Alkabie, D. Carapic, D. S.-H. Shin, and L.T. Buck. 2008. Evidence of anoxia-induced channel arrest in the brain of the goldfish (Carassius auratus). Comparative Biochemistry and Physiology Part A. 148C:355-362.

Wilkie, M.P., J.A. Holmes, and J.H. Youson. 2007. The lampricide, 3-trifluoromethyl-4-nitrophenol (TFM) interferes with intermediary metabolism and glucose homeostasis, but not ion balance in larval lampreys (Petromyzon marinus). Canadian Journal of Fisheries & Aquatic Sciences 64:1174-1182.

Wilkie, M.P., T.P. Morgan, F. Galvez, R.W. Smith, M. Kajimura, Y.K. Ip, and C.M. Wood. 2007. The African lungfish (Protopterus dolloi): Ionoregulation and osmoregulation in a fish out of water. Physiological and Biochemical Zoology 80:99-112.

Walsh, P.J., C.M. Veauvy, M.D. McDonald, M.E. Pamenter, L.T. Buck, and M.P. Wilkie. 2007. Piscine insights into comparisons of anoxia tolerance, ammonia toxicity, stroke and hepatic encephalopathy. Comparative Biochemistry and Physiology, Part A. 147:332-343.

Wilkie, M.P., J.F. Claude, A. Cockshutt, J.A. Holmes, Y.S. Wang, J.H. Youson and P.J. Walsh. 2006. Shifting patterns of nitrogenous waste excretion and amino acid catabolism capacity during the life cycle of the sea lamprey (Petromyzon marinus). Physiological and Biochemical Zoology. 79:885-898.

Shin, D.S., M.P. Wilkie, M.E. Pamenter, and L.T. Buck. 2005. Calcium and protein phosphatase 1 and 2A attenuate N-methyl-D aspartate receptor activity in the anoxic turtle cortex. Comparative Biochemistry and Physiology, Part A. 142:50-57.

Wilkie, M.P., S. Turnbull, J. Bird, Y. S. Wang, J.F. Claude, and J.H. Youson. 2004. Lamprey parasitism of sharks and teleosts: high capacity urea excretion in an extant vertebrate relic. Comparative Biochemistry and Physiology, Part A 138:485-492.

Wilkie, M.P., J.G. Wigmore, and J.W. Patrick. 2003. The performance of the approved screening device, the Alcotest 7410 GLC in the field: Low incidence of false positive results in the identification of drinking drivers. Canadian Society of Forensic Science Journal 36:165-171.

Wilkie, M.P. 2002. Ammonia excretion and urea handling by fish gills: present understanding and future research challenges. Invited review article included in a special edition of the Journal of Experimental Zoology entitled “Anatomy and Physiology of the Fish Gill: A Prospective Approach.” David H. Evans and Kenneth R. Olson eds. 293:284-301.

Wigmore, J.G., and M.P. Wilkie. 2002. A simulation of the effect of blood in the mouth on breath alcohol concentrations of drinking subjects. Canadian Society of Forensic Science Journal 35:9-16.

Wilkie, M.P., P.G. Bradshaw, V. Joanis, J.F. Claude, and S.L. Swindell. 2001. Rapid metabolic recovery following vigorous exercise in burrow-dwelling larval sea lampreys (Petromyzon marinus). Physiological and Biochemical Zoology 74:261-272.

Laurent, P., M.P. Wilkie, C. Chevalier, and C.M. Wood. 2000. The effect of highly alkaline water (pH=9.5) on the morphology and morphometry of chloride cells and pavement cells in the gills of the freshwater rainbow trout: relationship to ion transport and ammonia excretion. Canadian Journal of Zoology 78:307-319.

Wilkie, M.P., Y. Wang, P.J. Walsh and J.H. Youson. 1999. Nitrogenous waste excretion by the larvae of a phylogenetically ancient vertebrate: the sea lamprey (Petromyzon marinus). Canadian Journal of Zoology 77: 707-715.

Wilkie, M.P., P. Laurent, and C.M. Wood. 1999. The physiological basis for altered Na+ and Cl- movements across the gills of rainbow trout in highly alkaline (pH 9.5) water. Physiological and Biochemical Zoology 72:360-368.

Wilkie, M.P., J. Couturier, and B.L. Tufts. 1998. Mechanisms of acid-base regulation in migrant sea lampreys (Petromyzon marinus) following exhaustive exercise. Journal of Experimental Biology 201:1473-1482.

Wilkie, M.P. 1997. Mechanisms of ammonia excretion across fish gills. Invited Review. Comparative Biochemistry and Physiology 118A:39-50.

Wilkie, M.P., M.A. Brobbel, L. Forsyth, K. Davidson and B.L. Tufts. 1997. The influence of temperature on the post-exercise physiology and survival of Atlantic salmon (Salmo salar). Canadian Journal of Fisheries and Aquatic Sciences 54:503-511.

Marshall, W.S., S.E. Bryson, P. Darling, C. Whitten, M.L. Patrick, M.P. Wilkie, C.M. Wood and J. Buckland-Nicks. 1997. NaCl transport and ultrastructure of opercular epithelium from a freshwater-adapted euryhaline teleost, Fundulus heteroclitus. Journal of Experimental Zoology 277:23-37.

Iwama, G.K., J.C. McGeer, P.A. Wright, M.P. Wilkie, and C.M. Wood. 1997. Divalent cations enhance ammonia excretion in Lahontan cutthroat trout (Oncorhynchus clarki henshawi) in highly alkaline water. Journal of Fish Biology 50:1061-1073.

Wilkie, M.P. and C.M. Wood. 1996. The adaptations of fish to extremely alkaline environments. Paper presented by M.P. Wilkie at the European Society for Comparative Physiology and Biochemistry Congress focusing on "Life in Extreme Environments". La Seyne-sur-Mer, France. June 1995. Comparative Biochemistry and Physiology 113B:665-673.

Brobbel, M.A., M.P. Wilkie, K. Davidson, J. D. Kieffer, A.T. Bielak and B.L. Tufts. 1996. Physiological effects of catch and release angling in Atlantic salmon (Salmo salar) at different stages of freshwater migration. Canadian Journal of Fisheries and Aquatic Sciences 53:2036-2043.

Wilkie, M.P., K. Davidson, M.A. Brobbel, J.D Kieffer, R.J. Booth, A. Bielak and B.L. Tufts. 1996. Physiology and survival of wild Atlantic salmon following angling in warm summer waters. Transactions of the American Fisheries Society 125:572-580.

Wilkie, M.P., H.E. Simmons and C.M. Wood. 1996. Physiological adaptations of rainbow trout to chronically elevated water pH (pH= 9.5). Journal of Experimental Zoology 274:1-14.

Wilkie, M.P. and C.M. Wood. 1995. Recovery from high pH exposure in the rainbow trout: white muscle ammonia storage, ammonia washout and the restoration of blood chemistry. Physiological Zoology 68:379-401.

Wang, Y., M.P. Wilkie, G.J.F. Heigenhauser and C.M. Wood. 1994. The analysis of metabolites in rainbow trout white muscle: a comparison of different sampling and processing methods. Journal of Fish Biology 45:855-873.

Wilkie, M.P., P.A. Wright, G.K. Iwama and C.M. Wood. 1994. The physiological adaptations of the Lahontan cutthroat trout (Oncorhynchus clarki henshawi) to the highly alkaline (pH = 9.4) waters of Pyramid Lake, Nevada. Physiological Zoology 67:355-380.

Wilkie, M.P., and C.M. Wood. 1994. The effects of extremely alkaline water (pH 9.5) on rainbow trout gill function and morphology. Journal of Fish Biology 45:87-98.

McGeer, J.C., P.A. Wright, C.M. Wood, M.P. Wilkie, C.F. Mazur and G.K. Iwama. 1994. Nitrogen excretion in four species of fish from an alkaline/saline lake. Transactions of the American Fisheries Society 123:824-829.

Wilkie, M.P., P.A. Wright, G.K. Iwama and C.M. Wood. 1993. The physiological resistance of the Lahontan cutthroat trout (Oncorhynchus clarki henshawi), a resident of highly alkaline (pH = 9.4) Pyramid Lake, to challenge at pH 10. Journal of Experimental Biology 175:173-194.

Wilkie, M.P. and C.M. Wood. 1991. Nitrogenous waste excretion, acid-base regulation and ionoregulation in rainbow trout (Oncorhynchus mykiss) exposed to extremely alkaline water. Physiological Zoology 64:1069-1086.

Graduate

• 2015 - present BI601. Research in Integrative Biology

Undergraduate

• 2016 - present WASC101: Global Issues in Water & Environmental Health
• 2015 (Fall) BI300 Environmental Toxicology (substitute: September – mid-October)
• 2015 (Winter) BI456 Physiological Adaptations to the Environment in Animals
• 2015 (Winter) BI217 Human Physiology II – Structure, Function and Integration