Professor David Hazlerigg
Chair in Zoology
1989 BSc Applied Biology - University of Bath
1993 PhD Cellular actions of melatonin - University of Cambridge
I am interested in the mechanisms animals use to deal with predictable environmental changes based on geophysical cycles (Earth's rotation and orbit of the Sun, and the Moon's orbit of the Earth). Organisms have evolved biological clocks to synchronise to these cycles, and hence to predict temporal sequences of environmental change.
Intense research in this area has defined the mechanisms through which organisms generate endogenous “circadian” (= of approximately 24-h period length) rhythms in behaviour and physiology. The prevailing view is that cells throughout organisms can behave as autonomous circadian oscillators, but require synchronisation by a pacemaker in order that they coordinate their activities effectively. In mammals this circadian pacemaker lies in a region of the brain known as the suprachiasmatic nucleus, and is synchronised to the daily light-dark cycle through the retina.
The daily light-dark cycle is also crucial for the synchronisation of long term seasonal cycles of physiology - for example transitions between breeding and non-breeding condition, winter hibernation and migration. Here, day-length (known as photoperiod) acts as a major synchonising cue for endogenous long term seasonal timing processes.
In mammals, expression of seasonal changes in physiology depends largely on changes in the function of the hypothalamus and pituitary gland, which act jointly through changes in nervous and hormonal outputs to affect a host of physiological attributes of the animal. For instance, reproductive activation, seasonal moulting of fur and changes in appetite all derive from changes in hypothalamic and pituitary activity.
My current research programme is directed towards understanding how photoperiod drives long term changes in hypothalamic and pituitary function in seasonal mammals, focussing on the central role that the pineal hromone melatonin plays in this process.
Recent collaborators include:
Gerald Lincoln - University of Edinburgh
Bruce Whitelaw - Roslin Institute, University of Edinburgh
Mick Hastings - LMB, Cambridge
Roelof Hut - University of Groningen
Mireille Pevet - Universite Louis Pasteur, Strasbourg
2008 - BBSRC - "Thyrotrophin signaling at the core of photoperiodic timing "
2007 - BBSRC - "Defining the molecular basis of photoperiodism in mammals"
2006 - The Royal Society- "Evolution and Photoperiodism in the 3-spined stickleback"
2004 - BBSRC - “Melatonin action in mammals: from coincidence to amplitude"
2004 - BBSRC (Strategic Studentship Scheme) - “Photoperiodism and migration in the stickleback: the mechanistic basis to physiological variation”
Contributions to Journals
- Krol, E., Douglas, A., Dardente, H., Birnie, M., van der Vinnie, V., Eijer, W., Gerkema, M., Hazlerigg, DG. & Hut, R. (2012). 'Strong pituitary and hypothalamic responses to photoperiod but not to 6-methoxy-2-benzoxazolinone in female common voles (Microtus arvalis)'. General and Comparative Endocrinology, vol 179, no. 2, pp. 289-295.
[Online] DOI: 10.1016/j.ygcen.2012.09.004
- Ebenhöh, O. & Hazlerigg, D. (in press). 'Modelling a molecular calendar: the seasonal photoperiodic response in mammals'. Chaos, Solitons and Fractals.
- Hanon, EA., Routledge, KW., Dardente, H., Masson-Pevet, M., Morgan, PJ. & Hazlerigg, DG. (2010). 'Effect of Photoperiod on the Thyroid-Stimulating Hormone Neuroendocrine System in the European Hamster (Cricetus cricetus)'. Journal of Neuroendocrinology, vol 22, no. 1, pp. 51-55.
[Online] DOI: 10.1111/j.1365-2826.2009.01937.x
- Dardente, H., Wyse, CA., Birnie, MJ., Dupre, SM., Loudon, ASI., Lincoln, GA. & Hazlerigg, DG. (2010). 'A Molecular Switch for Photoperiod Responsiveness in Mammals'. Current Biology, vol 20, no. 24, pp. 2193-2198.
[Online] DOI: 10.1016/j.cub.2010.10.048
- Fustin, JM., Dardente, H., Wagner, GC., Carter, DA., Johnston, JD., Lincoln, GA. & Hazlerigg, DG. (2009). 'Egr1 involvement in evening gene regulation by melatonin'. FASEB Journal, vol 23, no. 3, pp. 764-773.
[Online] DOI: 10.1096/fj.08-121467
- Dardente, H., Birnie, M., Lincoln, GA. & Hazlerigg, DG. (2008). 'RFamide-Related Peptide and its Cognate Receptor in the Sheep: cDNA Cloning, mRNA Distribution in the Hypothalamus and the Effect of Photoperiod'. Journal of Neuroendocrinology, vol 20, no. 11, pp. 1252-1259.
[Online] DOI: 10.1111/j.1365-2826.2008.01784.x
- Hanon, EA., Lincoln, GA., Fustin, J-M, Dardente, H., Masson-Pevet, M., Morgan, PJ. & Hazlerigg, DG. (2008). 'Ancestral TSH mechanism signals summer in a photoperiodic mammal'. Current Biology, vol 18, no. 5, pp. 1147-1152.
[Online] DOI: 10.1016/j.cub.2008.06.076
- Audinot, V., Bonnaud, A., Grandcolas, L., Rodriguez, M., Nagel, N., Galizzi, J-P, Balik, A., Messager, S., Hazlerigg, DG., Barrett, P., Delagrange, P. & Boutin, JA. (2008). 'Molecular cloning and pharmacological characterization of rat melatonin MT1 and MT2 receptors'. Biochemical Pharmacology, vol 75, no. 10, pp. 2007-2019.
[Online] DOI: 10.1016/j.bcp.2008.02.022
- Wagner, GC., Johnston, JD., Clarke, IJ., Lincoln, GA. & Hazlerigg, DG. (2008). 'Redefining the limits of day length responsiveness in a seasonal mammal'. Endocrinology, vol 149, no. 1, pp. 32-39.
[Online] DOI: 10.1210/en.2007-0658
- Karamanlidis, G., Karamitri, A., Docherty, K., Hazlerigg, DG. & Lomax, MA. (2007). 'C/EBPß Reprograms White 3T3-L1 Preadipocytes to a Brown Adipocyte Pattern of Gene Expression'. Journal of Biological Chemistry, vol 282, pp. 24660-24669.
[Online] DOI: 10.1074/jbc.M703101200
- Johnston, JD., Schuster, C., Barrett, P. & Hazlerigg, DG. (2007). 'Regulation of the ovine MT1 melatonin receptor promoter: Interaction between multiple pituitary transcription factors at different phases of development'. Molecular and Cellular Endocrinology, vol 268, no. 1-2, pp. 59-66.
[Online] DOI: 10.1016/j.mce.2007.01.015
- Wagner, GC., Johnston, JD., Tournier, BB., Ebling, FJP. & Hazlerigg, DG. (2007). 'Melatonin induces gene-specific effects on rhythmic mRNA expression in the pars tuberalis of the Siberian hamster (Phodopus sungorus)'. European Journal of Neuroscience, vol 25, no. 2, pp. 485-490.
[Online] DOI: 10.1111/j.1460-9568.2006.05291.x
- Johnston, JD., Klosen, P., Barrett, P. & Hazlerigg, DG. (2006). 'Regulation of MT1 melatonin receptor expression in the foetal rat pituitary'. Journal of Neuroendocrinology, vol 18, no. 1, pp. 50-56.
[Online] DOI: 10.1111/j.1365-2826.2005.01389.x
- Johnston, JD., Messager, S., Ebling, FJP., Williams, LM., Barrett, P. & Hazlerigg, DG. (2003). 'Gonadotrophin-releasing hormone drives melatonin receptor down-regulation in the developing pituitary gland'. PNAS, vol 100, no. 5, pp. 2831-2835.
[Online] DOI: 10.1073/PNAS.0436184100
- Hazlerigg, DG. (2003). 'Melatonin Action in the Pituitary: Neuroendocrine Synchronizer and Developmental Modulator?'. Journal of Neuroendocrinology, vol 15, pp. 405-408.
[Online] DOI: 10.1046/j.1365-2826.2003.01094.x
- Hazlerigg, DG. (2002). 'Evidence for the Biosynthesis of a Prolactin-Releasing Factor From the Ovine Pars Tuberalis, Which is Distinct from Thyrotropin-Releasing Hormone'. Journal of Neuroendocrinology, vol 14, pp. 945-954.
[Online] DOI: 10.1046/j.1365-2826.2002.00848.x
- Lincoln, G., Messager, S., Andersson, H. & Hazlerigg, DG. (2002). 'Temporal expression of seven clock genes in the suprachiasmatic nucleus and the pars tuberalis of the sheep: Evidence for an internal coincidence timer'. PNAS, vol 99, no. 21, pp. 13890-13895.
[Online] DOI: 10.1073/pnas.212517599
- Barrett, P., Davidson, G., Hazlerigg, DG., Morris, A., Ross, A. & Morgan, PJ. (1998). 'Mel 1a melatonin receptor expression is regulated by protein kinase C and an additional pathway addressed by the protein kinase C inhibitor Ro 31-8220 in ovine pars tuberalis cells'. Endocrinology, vol 139, no. 1, pp. 163-171.
[Online] DOI: 10.1210/en.139.1.163
- Hazlerigg, DG., Barrett, P., Hastings, MH. & Morgan, PJ. (1996). 'Are nuclear receptors involved in pituitary responsiveness to melatonin?'. Molecular and Cellular Endocrinology, vol 123, no. 1, pp. 53-59.
[Online] DOI: 10.1016/0303-7207(96)03900-7
- Morgan, PJ., Webster, CA., Mercer, J., Ross, A., Hazlerigg, DG., MacLean, A. & Barrett, P. (1996). 'The ovine pars tuberalis secretes a factor(s) that regulates gene expression in both lactotropic and nonlactotropic pituitary cells'. Endocrinology, vol 137, no. 9, pp. 4018-4026.
[Online] DOI: 10.1210/en.137.9.4018
- Morgan, PJ., Barrett, P., Hazlerigg, DG., MILLIGAN., G., LAWSON, W., MACLEAN, A. & DAVIDSON, G. (1995). 'Melatonin Receptors Couple Through a Cholera Toxin-Sensitive Mechanism to Inhibit Cyclic AMP in the Ovine Pituitary'. Journal of Neuroendocrinology, vol 7, no. 5, pp. 361-369.
[Online] DOI: 10.1111/j.1365-2826.1995.tb00770.x
- Morgan, PJ., Barrett, P., DAVIDSON., G., LAWSON, W. & Hazlerigg, DG. (1994). 'p72, a Marker Protein for Melatonin Action in Ovine Pars tuberalis Cells'. Neuroendocrinology, vol 59, no. 4, pp. 325-335.
[Online] DOI: 10.1159/000126674
- Morgan, PJ. & Hazlerigg, DG. (2008). 'Photoperiodic signalling through the melatonin receptor turns full circle'. Journal of Neuroendocrinology, vol 20, no. 6, pp. 820-826.
[Online] DOI: 10.1111/j.1365-2826.2008.01724.x
- Hazlerigg, DG. & Wagner, GC. (2006). 'Seasonal photoperiodism in vertebrates: from coincidence to amplitude'. Trends in Endocrinology and Metabolism, vol 17, pp. 83-91.
[Online] DOI: 10.1016/j.tem.2006.02.004
- Hazlerigg, DG. (2003). 'You probably can't afford it, but can you afford to ignore it?'. Journal of Neuroendocrinology, vol 15, pp. 905-906.
[Online] DOI: 10.1046/j.1365-2826.2003.01094.x
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