Professor David Hazlerigg
Chair in Zoology
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+44 (0)1224 272871
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d.hazlerigg@abdn.ac.uk
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School of Biological Sciences
rm 309 Zoology Building,
Tillydrone Avenue
Aberdeen
Chair in Zoology
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Personal Details
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Biography
1989 BSc Applied Biology - University of Bath
1993 PhD Cellular actions of melatonin - University of Cambridge
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Research Interests
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.
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Collaborations
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
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Research Grants
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”
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Selected Publications
Fustin JM, O'Neill JS, Hastings MH, Hazlerigg DG, Dardente H (2009) Cry1 Circadian Phase in vitro: Wrapped Up with an E-box. Journal of Biological Rhythms 24: 16-24
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 23:764-773
Dardente HD, Mendoza J, Fustin J-M, Challet E, Hazlerigg DG (2008) Implication of the F-box protein Fbxl21 in circadian pacemaker function in mammals. PLoS ONE 3(10):e3530
Hazlerigg DG, Loudon ASI (2008) Seasonal life timers in mammals: new insights into ancient mechanisms. Current Biology 18:R795-R804
Dardente H, Lincoln GA, Birnie M, Hazlerigg DG (2008) RFamide-related peptide and its cognate receptor in the sheep: cDNA cloning, mRNA distribution in the hypothalamus and effect of photoperiod. Journal of Neuroendocrinology 20: 1252-1259
Hanon E, Lincoln GA, Fustin J-M, Dardente H, Masson-Pevet M, Morgan PJ, Hazlerigg DG (2008) Ancestral TSH mechanism signals summer in a seasonal mammal. Current Biology 18:1147-1152
Morgan PJ, Hazlerigg DG (2008) Photoperiodic signalling through the melatonin receptor turns full circle. Journal of Neuroendocrinology 20: 820-826.
Wagner GC, Johnston, JD; Clarke, IJ, Lincoln GA, Hazlerigg DG (2008) Redefining the limits of day length responsiveness in a seasonal mammal. Endocrinology 149: 32-39.
Karamanlidis G, Karamitri A, Docherty K, Hazlerigg DG, Lomax MA (2007) C/EBP beta reprograms white 3T3-L1 preadipocytes to a brown adipocyte pattern of gene expression. Journal of Biological Chemistry 282:24660-24669.
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. Mol Cell Endocrinol 268:59-66.
Sadiq F, Hazlerigg DG, Lomax MA (2007) Amino acids and insulin act additively to regulate components of the ubiquitin-proteasome pathway in C2C12 myotubes BMC Molecular Biology 8: Art. No. 23
Lincoln GA, Clarke IJ, Hut RA, Hazlerigg DG (2006) Characterizing a mammalian circannual pacemaker. Science 314: 1941-1944
Hazlerigg DG, Wagner GC (2006) Seasonal photoperiodism in vertebrates: from coincidence to amplitude. Trends in Endocrinology and Metabolism 17 :83-91
Johnston JD, Klosen P, Barrett P, Hazlerigg DG (2006) Regulation of MT1 Melatonin Receptor Expression in the Foetal Rat Pituitary. Journal of Neuroendocrinology 18:50-56
Johnston JD, B Tournier B, Andersson H, Masson-Pévet M, Lincoln GA, Hazlerigg DG (2006) Multiple effects of melatonin on rhythmic clock gene expression in the mammalian pars tuberalis Endocrinology 147:959-965
Lincoln GA, Johnston JD, Andersson H, Wagner G, Hazlerigg DG (2005): Photorefractoriness in mammals: Dissociating a seasonal timer from the circadian-based photoperiod response Endocrinology 146: 3782-3790
Hazlerigg DG, Ebling FJP, Johnston JD (2005) Photoperiod differentially regulates rhythms of gene expression in the Rostral and Caudal Suprachiasmatic Nuclei. Current Biology 15 R449-R450
Andersson H, Johnston JD, Messager S, Hazlerigg D, Lincoln G (2005) Photoperiod regulates clock gene rhythms in the ovine liver. General & Comparative Endocrinology 142:357-363
Johnston JD, Ebling FJP, Hazlerigg DG (2005) Photoperiod regulates multiple gene expression in the suprachiasmatic nuclei and pars tuberalis of the Siberian hamster (Phodopus sungorus). European Journal of Neuroscience 21:2967-2974
Hazlerigg DG, Andersson H, Johnston JD, Lincoln GA (2004) Molecular characterisation of the long day response in the Soay sheep, a seasonal mammal. Current Biology 14:334-339
Johnston JD, Bashforth R, Diak A, Andersson H, Lincoln GA, Hazlerigg DG (2004) Rhythmic melatonin secretion does not correlate with the expression of arylalkylamine N-acetyl transferase, inducible cyclic adenosine monophosphate early repressor, period1 or cryptochrome1 mRNA in the sheep pineal. Neuroscience 124: 789-795
Hazlerigg D (2003) You probably can't afford it, but can you afford to ignore it? Journal of Neuroendocrinology 15 (10): 905-906
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. Proceedings of the National Academy of Sciences USA 100:2831-2835
Johnston JD, Messager S, Barrett P, J Hazlerigg DG (2003) Melatonin action in the anterior pituitary: neuroendocrine synchroniser and developmental modulator? Journal of Neuroendocrinology 15:405-408
Lincoln GA, Andersson H, Hazlerigg DG (2003) Clock genes and the long term regulation of prolactin secretion: evidence for a photoperiod / circannual timer in the pars tuberalis. Journal of Neuroendocrinology 15:390-397
Lincoln GA, Messager S, Andersson H, Hazlerigg DG (2002) Temporal expression of seven clock genes in the suprachiasmatic nuclei and the pars tuberalis of the sheep: Evidence for an internal coincidence timer. Proceedings of the National Academy of Sciences, USA 99:13890-13895
Stubbs AK, Wheelhouse NM, Lomax MA, Hazlerigg DG (2002) Nutrient – hormone interaction in the ovine liver: methionine supply selectively modulates growth hormone-induced IGF-1 gene expression. Journal of Endocrinology 174:335-341
Graham ES, Webster CA, Hazlerigg DG, Morgan PJ (2002) Evidence for the biosynthesis of a prolactin releasing factor from the ovine pars tuberalis, which is distinct from TRH. Journal of Neuroendocinology 14:945-954
Hazlerigg DG (2001) What is the role of melatonin in the anterior pituitary? Journal of Endocrinology 170:493-501
Hazlerigg DG, Messager S, Morgan PJ (2001) Decoding photoperiodic time and melatonin in mammals: what can we learn from the pars tuberalis? Journal of Biological Rhythms 16:326-335
Messager S, Garabette ML, Hastings MH, Hazlerigg DG (2001) Tissue-specific abolition of Per1 expression in the pars tuberalis by pinealectomy in the Syrian hamster. Neuroreport 12:579-582
Messager S, Hazlerigg DG, Mercer JG, Morgan PJ (2000) Photoperiod differentially regulates the expression of Per1 and ICER in the pars tuberalis and the suprachiasmatic nucleus of the Siberian hamster. European Journal of Neuroscience 12:2865-2870
Wheelhouse NM, Stubbs AK, Lomax MA, MacCrae JC, Hazlerigg DG (1999) Growth hormone and amino acid supply interact synergistically to control insulin-like growth factor-1 production and gene expression in cultured ovine hepatocytes. Journal of Endocrinology 163:353-361
Graham ES, Hazlerigg DG, Morgan PJ (1999) Evidence for regulation of basic fibroblast growth factor gene expression by photoperiod and melatonin in the ovine pars tuberalis. Molecular & Cellular Endocrinology 156:45-53
Barrett P, Davidson G, Hazlerigg DG, Morris MA, Ross AW, 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 139:163-171.
Hazlerigg DG, Morgan PJ (1997) The Pars tuberalis - A pituitary target for melatonin. Frontiers of Hormone Research 23:3-13.
Hazlerigg DG, Barrett P, Hastings MH and Morgan PJ (1996) Are nuclear receptors involved in pituitary responsiveness to melatonin? Molecular and Cellular Endocrinology 123:53-59.
Morgan PJ, Webster CA, Mercer JG, Ross AW, 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 137:4018-4026.
Hazlerigg DG, Hastings MH, Morgan PJ (1996) Production of a prolactin releasing factor by the ovine pars tuberalis. Journal of Neuroendocrinology 8:489-492
Thompson MG, Mackie SC, Thom A, Hazlerigg DG, Morrison KS, Palmer RM (1996) Cyclic AMP stimulates protein synthesis in L6 myoblasts and its effects are additive to those of insulin, vasopressin and 12-0-tetradecanoylphorbol-13-acetate. Possible involvement of mitogen activated protein kinase. Biochimica et Biophysica Acta - molecular cell research 1311:37-44.
Hazlerigg DG, Thompson M, Hastings MH, Morgan PJ (1996) Regulation of mitogen-activated protein kinase in the pars tuberalis of the ovine pituitary: interactions between melatonin, insulin-like growth factor-1 and forskolin. Endocrinology 137: 210-218
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 cAMP in the ovine pituitary. Journal of Neuroendocrinology.7:361-369.
Hazlerigg DG, Hastings MH, Morgan PJ (1994) The recovery of ovine pars tuberalis cells from melatonin-induced sensitization is a slow protein-synthesis dependent phenomenon. J Endocrinology 142:127-138
Morgan PJ, Barrett P, Davidson G, Lawson W, Hazlerigg DG (1994) P72, a marker protein for melatonin action in ovine pars tuberalis cells and differential secretion relative to prolactin. Neuroendocrinology59:325-335.
Hazlerigg DG, Morgan PJ, Hastings MH (1994) Melatonin-induced sensitization of ovine pars tuberalis cells. Advances in Pineal Research 8:371-376.
Hazlerigg DG, Gonzalez-Brito A, Lawson W, Hastings MH, Morgan PJ (1993) Prolonged exposure to melatonin leads to time-dependent sensitization of adenylate cyclase and down-regulates melatonin receptors in pars tuberalis cells from ovine pituitary. Endocrinology 132: 285-292.
Hazlerigg DG, Morgan PJ, Lawson W, Hastings MH (1991) Melatonin inhibits the activation of cyclic AMP-dependent protein kinase in cultured pars tuberalis cells from ovine pituitary. J Neuroendocrinology 3:597-603.
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