Evolution of Cardiac Design in Vertebrates
Funding: Project available for individuals with self arranged funding.
The vertebrate heart has evolved from the 2 chambered fish heart to the 4 chambered mammalian/bird heart. Associated with the change in chamber morphology are important changes in heart function. Cardiac function in fish, amphibians and reptiles is controlled, to a large extent, via mechanical regulation (i.e. stretch). In contrast bird and mammals tend to be less stretch modulated and more frequency modulated in terms of function. Indeed, the fish and turtle hearts can expand more than 300% to accommodate large changes in blood volume where as birds and increase heart rate 600%! This PhD project will look role of mechano-electric feedback on vertebrate hearts, and the active and passive properties of the cells that make up these hearts. The project will involve in vivo measurements of cardiac function, and mechanical and electrical studies of isolated whole hearts and cardiac myocytes. The student will learn electrophysiology, florescent imaging and cellular tension measurements. Studies will involve all vertebrate classes from fish, amphibians, reptiles, birds and mammals. The work has both evolutionary and biomedical relevance.
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Patrick SM, White E, Shiels HA (2010) Mechano-Electric Feedback in the Fish Heart. PLoS ONE 5(5): e10548.
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2. Patrick, SM, Hoskins, A Kentish, J White E, Shiels, HA, and Cazorla, O. (2010) Enhanced length-dependent Ca2+ activation in fish cardiomyocytes permits a large operating range of sarcomere lengths. Journal of Molecular and Cellular Cardiology 48, 917-924..
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3. Shiels, HA, and White, E. (2008) The Frank Starling mechanism in vertebrate cardiac myocytes. Journal of Experimental Biology. 211, 2005-2013.
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4. Shiels, HA, Calaghan, SC and White, E. (2006). The cellular basis for enhanced volume-modulated cardiac output in fish hearts. Journal of General Physiology. 128, 37-44.
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Fish Cardiac Function in an Era of Climate Change
Funding: Project available for individuals with self arranged funding.
The warming of UK waterways associated with global climate change may be an important driver in the population decline and migration failures of native fish species. Rising water temperature and acidity may act on fish by negatively effecting cardiac function. The student will test this hypothesis across 4 levels of biological organisation. Studies will combine non-invasive whole animal physiology to assess aerobic scope using a swim flume respirometer, in situ whole heart and in vitro cardiac muscle and heart cell physiological analyses to reveal underlying mechanisms.
The student will be well-trained in whole-animal physiology which is widely recognized as an area requiring urgent investment. Upon conclusion, the student will have characterised the physiological events that limit performance of fish in response to climate change scenarios thus providing the student with a grounding in both animal physiology and climate change biology.
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Pörtner HO, Farrell AP. Ecology. Physiology and climate change. Science. 2008 Oct 31;322(5902):690-2.
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Hofmann, G.E. and Todgham, A.E. (2010). Living in the now: Physiological mechanisms to tolerate a rapidly changing environment. Annu. Rev. Physiol. 72: 127-145.
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Clark TD, Jeffries KM, Hinch SG and Farrell AP (2011) Exceptional aerobic scope and cardiovascular performance of pink salmon (Oncorhynchus gorbuscha) may underlie resilience in a warming climate. The Journal of Experimental Biology 214: 3074-3081.
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Eliason EJ, Clark TD, Hague MJ, Hanson LM, Gallagher ZS, Jeffries KM, Gale MK, Patterson DA, Hinch SG and Farrell AP (2011) Differences in thermal tolerance among sockeye salmon populations. Science 332: 109-112
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Petersen, L.H. and A. K. Gamperl. (2010). Effects of acute and chronic hypoxia on the swimming performance, metabolic capacity and cardiac function of Atlantic cod (Gadus morhua). J. Exp. Biol. 213: 808-819.
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J.C. Pérez-Casanova, L.O.B. Afonso, S. C. Johnson, S. Currie, and A.K. Gamperl (2008). The stress and metabolic response of Atlantic cod (Gadus morhua) to an acute thermal challenge. J. Fish Biol. 72: 889-916.
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Food chain transfer and toxicity of metallic nanoparticles in freshwater
Funding: Project available for individuals with self arranged funding.
Engineered metallic nanoparticles (NPs) are used widely in many industries and exposure to the consumer and to the environment is increasing, yet impacts are still unclear. Much research has focussed on exposure of individual organisms to single NPs and there has been no in depth examination of movement, behaviour and toxicity of NPs through the food chain, including transfer from algae to fish. Predicted exposure of humans is highest for silver (Ag)-NPs which are widely used due to their anti-bacterial properties. The overall aim of this studentship is to examine metallic NP accumulation and toxicity on three model species that form a freshwater food chain, and identify ecotoxicological effects of environmentally relevant concentrations of Ag-NP in comparison to the biologically inert titanium NP.
Algae form the basis of most aquatic food chains and are an entry point for NPs that may then transfer up the food chain via herbivorous crustacean and grazing fish. We have shown that Ag-NPs accumulate in the microalga Chlamydomonas and transfer into the zooplanktonic crustacean Daphnia through feeding on the algae. This studentship will perform an in depth analysis of NP accumulation, transfer and toxicity Chlamydomonas, Daphnia, and brown trout (Salmo trutta)
The specific aims of the project are:
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To characterise the mechanisms for Ag-NP accumulation into microalgae
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In comparison with Ti-NPs, quantify potential and characteristics for water-borne and diet-borne NPs to transfer into Daphnia, and brown trout
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To examine physiological indicators of NP toxicity in each model organism
The knowledge acquired from this study will provide an assessment of the risk of NP toxicity to the freshwater food chain and assist in the formulation of standards and guidelines relating to NP toxicity.
The student will receive training in algal culture, animal husbandry, trace metal analysis and behavioural measures of toxicity.
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McTeer, J, Dean, A P, White, K N & Pittman J K (submitted). Bioaccumulation of silver nanoparticles into Dapnia magna from a freshwater algal diet and the impact of phosphate concentration. Nanotechnology.
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Quiroz-Vazquez, P, Sigee, D C & White, K N (2010) Bioavailability and toxicity of aluminium in a model planktonic food-chain (Chlamydomonas-Daphnia) at neutral pH. Limnologica, 40, 269–277.
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Zebrafish hearts – basic physiology and role of adrenergic stimulation
Funding: Project available for individuals with self arranged funding.
Zebrafish have risen to prominence as a model organism for understanding complex biological phenomena like the cardiovascular system. Because zebrafish are genetically accessible vertebrates with a optically clear embryo, they are very popular for investigating genetic control of cardiac development. Despite this, almost nothing is known about the physiology of the zebrafish cardiac myocytes.
Stimulation of cardiac β adrenergic receptors (βARs) results in increased cardiac function in mammals but very little is known of βAR signalling in the zebrafish heart. This is becoming increasingly problematic as fish are a growing model for mammalian cardiac studies. This studentship is aimed at investigating, the physiology of zebrafish cardiac myocytes with a particular emphasis on β adrenergic stimulation.
The student will isolate cardiac myocytes from adult fish. They will then characterize their physiology using electrophysiology, video imaging and epi-florescent ion imaging and force measuremtns. All of the major ion pathways that are involved cellular Ca flux and myocyte excitation will be investigated using standard electrophysiological techniques. Video imaging via an edge-detection system will be combined with field stimulation to assess the contractile properties of the myocytes in response to known agonists and antagonists (i.e. adrenaline, adrenoreceptor inhibitors). This will be done at different stimulation frequencies to further characterise the contractile scope of these cells. The student will also use the calcium indicator dye Fura-2 to measure intracellular calcium transients in response to changing stimulation and agonists and antagonists. These will be the first studies to investigate the physiology of cardiac myocytes from the zebrafish. The possibility exists to extend these studies to mutant zebrafish lines.
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Brette, F, Luxan, G, Cros, C, Dixey,H, Wilson, C and Shiels, HA. (2008) Characterization of isolated ventricular myocytes from adult zebrafish (Danio rerio). Biochemical and Biophysical Research Communications. 374 , 143–146.
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Nemtsas P, Wettwer E, Christ T, Weidinger G, Ravens U. Adult zebrafish heart as a model for human heart? An electrophysiological study. J Mol Cell Cardiol. 2010 Jan;48(1):161-71. Epub 2009 Sep 8. PubMed PMID: 19747484.
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Steele, SL et al. (2011) In vivo and in vitro assessment of cardiac β-adrenergic receptors in larval zebrafish (Danio rerio) J Exp Biol 214, 1445-1457.
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Wang Z. et al (2009) Zebrafish β-adrenergic receptor mRNA expression and control of pigmentation. Gene Vol 446, 18-27.
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