Graham Scott, Ph.D.

Telephone: (905) 525-9140

Office: LSB – 227 Ext 26692

Lab: LSB – 203 Ext 27410



Interests & Activities

My lab strives to understand the integrative mechanisms (from molecule to organism) for how vertebrate animals tolerate and perform in challenging physical environments. We are interested in the physiological, cellular, and genomic bases of adaptation and acclimatization, particularly in response to hypoxia and/or temperature change. Physiological systems important for respiration and exercise are emphasized.


Publications in Review

  • Scott, G.R., T.S. Elogio, M.A. Lui, J.F. Storz, and Z.A. Cheviron. 2015. Adaptive modifications of muscle phenotype in high-altitude deer mice are associated with evolved changes in gene regulation.

Publications in Peer-Reviewed Journals

  • Lui, M.A., S. Mahalingam, P. Patel, A.D. Connaty, C.M. Ivy, Z.A. Cheviron, J.F. Storz, G.B. McClelland, and G.R. Scott. 2015. High-altitude ancestry and hypoxia acclimation have distinct effects on exercise capacity and muscle phenotype in deer mice. Am. J. Physiol. Reg. Integr. Comp. Physiol. In press.
  • Borowiec, B.G., K.L. Darcy, D.M. Gillette, and G.R. Scott. 2015. Distinct physiological strategies are used to cope with constant hypoxia and intermittent hypoxia in killifish (Fundulus heteroclitus). J. Exp. Biol. In press.
  • Ivy, C.M. and G.R. Scott. 2015. Control of breathing and the circulation in high-altitude mammals and birds. Comp. Biochem. Physiol. A. Mol. Integr. Physiol. In press.Scott, G.R., L.A. Hawkes, P.B. Frappell, P.J. Butler, C.M. Bishop, and W.K. Milsom. 2015. How bar-headed geese fly over the Himalayas. Physiology. 30, 107-115
  • Bishop, C.M., R.J. Spivey, L.A. Hawkes, N. Batbayar, B. Chua, P.B. Frappell, W.K. Milsom, T. Natsagdorj, S.H. Newman, G.R. Scott, J.Y. Takekawa, M. Wikelski, and P.J. Butler. 2015. The roller coaster flight strategy of bar-headed geese conserves energy during Himalayan migrations. Science. 347, 250-254.
  • Schnurr, M.E., Y. Yin, and G.R. Scott. 2014. Temperature during embryonic development has persistent effects on muscle energy metabolism in zebrafish. J. Exp. Biol. 217, 1370-1380.
  • Hawkes, L.A., S. Balachandran, N. Batbayar, P.J. Butler, B. Chua, D.C. Douglas, P.B. Frappell, Y. Hou, W.K. Milsom, S.H. Newman, D.J. Prosser, P. Sathiyaselvam, G.R. Scott, J.T. Takekawa, T. Natsagdorj, M. Wikelski, M.J. Witt, B. Yan, and C.M. Bishop. 2013. The paradox of extreme high altitude migration in bar-headed geese Anser indicus. Proc. R. Soc. B. In press.
  • Scott, G.R. and I.A. Johnston. 2012. Temperature during embryonic development has persistent effects on thermal acclimation capacity in zebrafish. Proc. Natl. Acad. Sci. 109, 14247-14252.
  • L.A. Hawkes, G.R. Scott, J.U. Meir, P.B. Frappell, and W.K. Milsom. 2011. Last Word on Point:Counterpoint: High altitude is/is not for the birds! J. Appl. Physiol. 111, 1525.
  • Scott, G.R., J.U. Meir, L.A. Hawkes, P.B. Frappell, and W.K. Milsom. 2011. Point: High altitude is for the birds! J. Appl. Physiol. 111, 1514-1519.
  • Scott, G.R. 2011. Elevated performance: the unique physiology of birds that fly at high altitudes. J. Exp. Biol. 214, 2455-2462.
  • Hawkes, L.A., S. Balachandran, N. Batbayar, P.J. Butler, P.B. Frappell, W.K. Milsom, N. Tseveenmyadag, S.H. Newman, G.R. Scott, P. Sathiyaselvam, J.T. Takekawa, M. Wikelski, and C.M. Bishop. 2011. The trans-Himalayan flights of bar-headed geese (Anser indicus). Proc. Natl. Acad. Sci. 108, 9516–9519.
  • Scott, G.R., P.M. Schulte, S. Egginton, A.L.M. Scott, J.G. Richards, and W.K. Milsom. 2011. Molecular evolution of cytochrome c oxidase underlies high-altitude adaptation in the bar-headed goose. Mol. Biol. Evol. 28, 351-363.
  • Matey, V., F.I. Iftikar, G. De Boeck, G.R. Scott, K.A. Sloman, V.M.F. Almeida-Val, A.L. Val, and C.M. Wood. 2011. Gill morphology and acute hypoxia: responses of mitochondria-rich, pavement, and mucous cells in two species with very different approaches to the osmo-respiratory compromise, the Amazonian oscar (Astronotus ocellatus) and the rainbow trout (Oncorhynchus mykiss). Can. J. Zool. 89, 307-324.
  • Storz, J.F., G.R. Scott, and Z.A. Cheviron. 2010. Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates. J. Exp. Biol. 213, 4125-4136.
  • Scott, G.R., J.G. Richards, and W.K. Milsom. 2009. Control of respiration in flight muscle from the high-altitude bar-headed goose and low-altitude birds. Am. J. Physiol. Reg. Integr. Comp. Physiol. 297, R1066–R1074.
  • Scott, G.R., S. Egginton, J.G. Richards, and W.K. Milsom. 2009. Evolution of muscle phenotype for extreme high altitude flight in the bar-headed goose. Proc. R. Soc. B. 276, 3645-3653.
  • Takekawa, J.Y., S.R. Heath, D.C. Douglas, W.M. Perry, S. Javed, S.H. Newman, R.N. Suwal, A.R. Rahmani, B.C. Choudhury, D.J. Prosser, B. Yan, Y. Hou, N. Batbayar, T. Natsagdorj, C.M. Bishop, P.J. Butler, P.B. Frappell, W.K. Milsom, G.R. Scott, L.A. Hawkes, and M. Wikelski. 2009. Geographic variation in bar-headed geese Anser indicus: connectivity of wintering areas and breeding grounds across a broad front. Wildfowl. 59, 100–123.
  • Sloman, K.A., R.D. Sloman, G. De Boeck, G.R. Scott, F.I. Iftikar, C.M. Wood, V.M.F. Almeida-Val, and A.L. Val. 2009. The role of size in synchronous air-breathing of Hoplosternum littorale. Physiol. Biochem. Zool. 82, 625-634.
  • Wood, C.M., F.I. Iftikar, G.R. Scott, G. De Boeck, K.A. Sloman, V. Matey, F.X. Valdez Domingos, R. Duarte, V.M.F. Almeida-Val, and A.L. Val. 2009. Regulation of gill transcellular permeability and renal function during acute hypoxia in the Amazonian oscar (Astronotus ocellatus): new angles to the osmo-respiratory compromise. J. Exp. Biol. 212, 1949-1964.
  • Lee, S.Y., G.R. Scott, and W.K. Milsom. 2008. Have wing morphology or flight kinematics evolved for extreme high altitude migration in the bar-headed goose? Comp. Biochem. Physiol. C. Pharmacol. Toxicol. 148, 324-331.
  • Scott, G.R., C.M. Wood, K.A. Sloman, F.I. Iftikar, G. De Boeck, V.M.F. Almeida-Val, and A.L. Val. 2008. Respiratory responses to progressive hypoxia in the Amazonian oscar, Astronotus ocellatus. Respir. Physiol. Neurobiol. 162, 109-116.
  • Scott, G.R., D.W. Baker, P.M. Schulte, and C.M. Wood. 2008. Physiological and molecular mechanisms of osmoregulatory plasticity in killifish after seawater transfer. J. Exp. Biol. 211, 2450-2459.
  • Singer, T.D., K.R. Keir, M. Hinton, G.R. Scott, R.S. McKinley, and P.M. Schulte. 2008. Structure and regulation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in killifish: a comparative genomics approach. Comp. Biochem. Physiol. D. Genomics Proteomics 3, 172-185.
  • Scott, G.R., V. Cadena, G.J. Tattersall, and W.K. Milsom. 2008. Body temperature depression and peripheral heat loss accompany the metabolic and ventilatory responses to hypoxia in low and high altitude birds. J. Exp. Biol. 211, 1326-1335.
  • Scott, G.R. and W.K. Milsom. 2007. Control of breathing and adaptation to high altitude in the bar-headed goose. Am. J. Physiol. Reg. Integr. Comp. Physiol. 293, R379-R391.
  • Wood, C.M., M. Kajimura, K.A. Sloman, G.R. Scott, P.J. Walsh, V.M.F Almeida-Val, and A.L. Val. 2007. Rapid regulation of Na+ fluxes and ammonia excretion in response to acute environmental hypoxia in the Amazonian oscar, Astronotus ocellatus. Am. J. Physiol. Reg. Integr. Comp. Physiol. 292, R2048-R2058.
  • Dodd, G.A.A., G.R. Scott, and W.K. Milsom. 2007. Ventilatory roll off during sustained hypercapnia is gender specific in pekin ducks. Respir. Physiol. Neurobiol. 156, 47-60.
  • Scott, G.R. and W.K. Milsom. 2006. Flying high: a theoretical analysis of the factors limiting exercise performance in birds at altitude. Respir. Physiol. Neurobiol. 154, 284-301.
  • Scott, G.R., P.M. Schulte, and C.M. Wood. 2006. Plasticity of osmoregulatory function in the killifish intestine: drinking rates, water transport, and gene expression after freshwater transfer. J. Exp. Biol. 209, 4040-4050.
  • Sloman, K.A., C.M. Wood, G.R. Scott, S. Wood, M. Kajimura, O.E. Johannsson, V.M.F. Almeida-Val, and A.L. Val. 2006. Tribute to R.G. Boutilier: The effect of size on the physiological and behavioural responses of oscar, Astronotus ocellatus, to hypoxia. J. Exp. Biol. 209, 1197-1205.
  • Scott, G.R., K.R. Keir, and P.M. Schulte. 2005. Effects of spironolactone and RU486 on gene expression and cell proliferation after freshwater transfer in the euryhaline killifish. J. Comp. Physiol. B. 175, 499-510.
  • Scott, G.R. and P.M. Schulte. 2005. Intraspecific variation in gene expression after seawater transfer in gills of the euryhaline killifish Fundulus heteroclitus. Comp. Biochem. Physiol. A. Mol. Integr. Physiol. 141, 176-182.
  • Scott, G.R., J.B. Claiborne, S.L. Edwards, P.M. Schulte, and C.M. Wood. 2005. Gene expression after freshwater transfer in gills and opercular epithelia of killifish: insight into divergent mechanisms of ion transport. J. Exp. Biol. 208, 2719-2729.
  • Scott, G.R., J.G. Richards, J.T. Rogers, C.M. Wood, and P.M. Schulte. 2004. Intraspecific divergence of ionoregulatory physiology in the euryhaline teleost Fundulus heteroclitus: possible mechanisms of freshwater adaptation. J. Exp. Biol. 207, 3399-3410.
  • Scott, G.R., J.G. Richards, B. Forbush, P. Isenring, and P.M. Schulte. 2004. Changes in gene expression in gills of the euryhaline killifish Fundulus heteroclitus after abrupt salinity transfer. Am. J. Physiol. Cell Physiol. 287, C300-C309.
  • Sloman, K.A., G.R. Scott, D.G. McDonald, and C.M. Wood. 2004. Diminished social status affects ionoregulation at the gills and kidney in rainbow trout (Oncorhynchus mykiss). Can. J. Fish. Aquat. Sci. 61, 618-626.
  • Scott, G.R. and K.A. Sloman. 2004. The effects of environmental pollutants on complex fish behaviour: integrating behavioural and physiological indicators of toxicity. Aquat. Toxicol. 68, 369-392.
  • Sloman, K.A., G.R. Scott, Z. Diao, C. Rouleau, C.M. Wood, and D.G. McDonald. 2003. Cadmium affects the social behaviour of rainbow trout, Oncorhynchus mykiss. Aquat. Toxicol. 65, 171-185.
  • Scott, G.R., K.A. Sloman, C. Rouleau, and C.M. Wood. 2003. Cadmium disrupts behavioural and physiological responses to alarm substance in juvenile rainbow trout (Oncorhynchus mykiss). J. Exp. Biol. 206, 1779-1790.

Book Chapters

  • Scott, G.R. and W.K. Milsom. 2009. Control of breathing in birds: implications for high altitude flight. In Cardio-Respiratory Control in Vertebrates: Comparative and Evolutionary Aspects (eds. M.L. Glass and S.C. Wood), pp. 429-448. Berlin: Springer-Verlag.

My research strives to understand how the respiratory and metabolic systems of vertebrates adjust to environmental change and how they adapt over evolutionary time. I use a comparative evolutionary approach in birds, mammals, and fish to understand the mechanistic basis for variation within and between vertebrate groups. Integrative approaches explore the causal links between levels of organization – from gene/genome to physiological system to organism.


The decline in oxygen (‘hypoxia’) at high altitudes is extremely challenging to terrestrial vertebrates. Oxygen levels atop the highest mountains in the world are scarcely sufficient to support life in many species – they are so low that unacclimatized lowland animals can be rendered comatose within minutes. However, every mountain range in the world contains species that are uniquely adapted to thrive at high altitudes. My research strives to explain the physiological mechanisms of adaptation and acclimatization to high-altitude hypoxia in birds and mammals. The emerging theme is that high-altitude species possess numerous mechanisms for matching O2 supply and O2 demand in hypoxia.

Previous work in this area focused on the bar-headed goose, a bird that flies over the Himalayas on its biannual migration between south and central Asia. The ability of this species to support the high metabolic rates needed for flight during high-altitude hypoxia is partially explained by enhancements in the O2 transport pathway, the physiological system important for supplying O2 from the air to every cell in the body (e.g., an enhanced hypoxic ventilatory response, large lungs, a high haemoglobin O2-affinity, and an increase in capillarity in the heart and flight muscle). This increase in O2 supply capacity is complemented by modifications in some of the traits that influence cellular O2 demands (e.g., kinetics of cytochrome c oxidase, mitochondrial regulation by creatine), whereas other features of O2 utilization are largely unaltered (e.g., metabolic capacity, mitochondrial O2 kinetics). These mechanistic discoveries were made by comparing closely related species raised in common conditions at sea level, and provided strong support for the role of adaptation in enabling performance during hypoxia.

Work in this area continues in other high-altitude mammals and birds. The mechanistic bases for adaptation and acclimatization to hypoxia are being explored to elucidate the general principles that unite or differentiate different highland species. This will help understand the influence of local hypoxia adaptation on altitudinal range shifts in response to climate change.


Hypoxia is prevalent in many aquatic environments. Freshwater, seawater, and estuarine environments can all exhibit variation in O2 levels as a result of both natural or anthropogenic causes. Nevertheless, fish can thrive in a range of hypoxic habitats in the wild. The integrative physiological basis of hypoxia tolerance and performance in fish is an important part of my research.

The unique physiological mechanisms exhibited by fish that can tolerate severe hypoxia have been actively studied for many years, including my past research and that of many others. It is clear that tolerant fish exhibit a range of strategies for matching O2 supply and O2 demand in hypoxia. My ongoing research in this area aims to understand the basis for variation in hypoxia tolerance in the wild. Of particular interest is how adaptation and/or acclimatization result in differences in tolerance and distribution in nature, whether there is variation between species in the effective strategies used for matching O2 supply (i.e., increases in flux through the O2 transport pathway) and O2 demand (i.e., metabolic depression) in hypoxia, how developmental stage affects the responses to hypoxia, and how environmental temperature interacts with hypoxia responses and tolerance. This work uses a comparative evolutionary approach to examine variation across closely related species, coupled with experiments that take advantage of the mechanistic tractability of the model species zebrafish. The ultimate goal is to understand the physiological basis for how different species with different tolerances are being affected by the growing prevalence of aquatic hypoxia in the wild.


Ectothermic animals are at the mercy of changes in environmental temperature, due in large part to the controlling effects of temperature on biological reaction rates. Although the mechanisms of temperature acclimation have been studied for decades, this research area is gaining renewed and vital importance as we seek to understand the biological effects of global warming. However, the majority of previous work in this area has focused on adult animals. My research in this area strives to understand how temperature change at different life stages affects exercise performance in fish. Of particular interest is how temperature during embryonic development influences thermal responses in adult fish. The mechanisms of thermal plasticity and acclimation capacity are examined in the physiological systems that support energy supply and demand during exercise (respiration, metabolism, muscle contraction, etc.).