Faculty of Biology, Medicine and Health

The University of Manchester

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  Zebrafish hearts – basic physiology and role of adrenergic stimulation

Prof Holly Shiels  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

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.

Funding Notes

To apply for this PhD project please see:
http://www.ls.manchester.ac.uk/phdprogrammes/howtoapply

References

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.

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.

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.

Wang Z. et al (2009) Zebrafish β-adrenergic receptor mRNA expression and control of pigmentation. Gene Vol 446, 18-27.


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Faculty of Biology, Medicine and Health

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