Prof. David G Hazlerigg




Current positions
2013 – Professor Department of Arctic and Marine Biology, UiT - The Arctic University of Norway, Tromsø


Research interests

I am a chronobiologist, with a specialist interest in the basic mechanisms underlying innate long-term, “circannual” timekeeping, their plasticity in the face of environmental change and their adaptive evolution. Circannual is an umbrella term for the internal timekeeping processes that ensure particular phases in an organism’s life history (growth, breeding, migration, hibernation, moult) occur at appropriate times of year. I focus on three avenues; Basic mechanisms, Plasticity and Evolution.


BASIC MECHANISMS: Defining core circannual timekeeping mechanisms
In mammals, pineal melatonin production provides a neurochemical representation of night length. I am interested in melatonin signal-processing mechanisms, and my work in seasonal mammals such as the Soay sheep has helped to define the current working model.



Photo from Gerald Lincoln




Here, the pars tuberalis (PT) of the pituitary transduces changes in melatonin signal duration into changing levels of thyrotrophin (TSH) secretion, which in turn controls thyroid hormone (TH) status in the neighbouring hypothalamus, via effects in specialised ependymal cells called “tanycytes”[1,2]. This in turn affects hypothalamic function leading to changes in endocrine and metabolic regulation.

Current attention focuses on the requirement for photoperiodic “history-dependence” in the circannual timer mechanism: seasonal synchronization by daylength must discriminate between increasing daylength in the spring and declining day length in the autumn.

My work on this subject focuses on maternal photoperiodic programming, the phenomenon through which the developmental trajectories of new born rodents are set by photoperiodic exposure in utero. With Valerie Simonneaux (CNRS, Strasbourg), I have shown that transplacental control of circannual state is mediated through maternal melatonin effects on the fetal PT / tanycyte, and that history-dependence is an emergent property of the fetal tanycytes [5]. I continue this work in collaboration with Valerie Simonneaux and Shona Wood.








PLASTICITY in circannual timekeeping in salmonids
Phenology is the study of the timing of seasonally cyclical natural phenomena. Phenology literature often neglects the concept of biologically innate timekeeping mechanisms and instead looks to direct correlations between annual cycles of physiology and behaviour and environmental variables. The correlative approach struggles with the observation that seemingly similar species or populations can show highly divergent responses to environmental variation. From an eco-physiological perspective, the obvious question is why do species vary in their capacity to adjust the seasonal timing of key activities (plasticity), when proper synchronisation is of such importance for Fitness?




Artwork by Jaymie van Delum
 
To address this question, I focus on salmonids [6], a recently diverged family of teleosts of vast global economic and cultural importance, with a temperate to polar geographic distribution. The salmonids typically undergo dramatic shifts in physiology (migration, growth, reproduction). The successful completion of these transitions is critically important in wild and farmed contexts, making the study of plasticity of timekeeping particularly relevant. Ongoing work led by Even Jørgensen and myself, and in collaboration with a wider group of national and international partners, focusses on a newly discovered cohort of genes for which appropriate timing of expression depends critically on prolonged exposure to winter photoperiods. The physiological causes and consequences of this “winter dependent” regulation are our main priorities.


EVOLUTION: Comparative genomics approaches to circannual timekeeping in birds and mammals
A weakness of current understanding of circannual timekeeping in mammals, and in birds (which share a broadly conserved PT-TSH-tanycyte-dio pathway with mammals), is that it is entirely based on descriptive (transcriptomic) approaches. This is in stark contrast to the sister discipline of circadian biology, for which mutagenesis-based forward genetic approaches have given massive leverage to modern understanding. Such an approach is not feasible over circannual timescales. The alternative is to exploit “natural experiments” in evolution where adaptive changes within the circannual machinery are predicted. To develop this avenue we focus on voles (g. Microtus) and the ptarmigan (g. Lagopus). The rock ptarmigan (L. muta) is a galliform bird with a holarctic distribution, and has a remarkably wide latitudinal range , with subspecies found as far north as Svalbard (80°N) and as far south as the Alps (@ 40°N). Through a RANNIS (https://www.rannis.is/) arctic studies grant, I have established links with European ptarmigan specialists from France, Norway, Iceland and Sweden, to screen for latitudinally based differences in seasonal clockwork. Through collaboration with Roelof Hut and Louis van de Zande at the University of Groningen (NL), we are conducting a similar exercise on evolutionary adaptation in voles (M. oeconomus, M arvalis), which also show a wide holarctic distribution with isolated variant populations. Linking genetics to functional differences in seasonal timekeeping is our strategic goal.









My work is supported by the Norwegian research council, the Human Frontiers Science Program and the Tromsoforskningstifelse.
 
 
  

References
  1. Hanon EA, Lincoln GA, Fustin J-M, Dardente H, Masson-Pévet M, Morgan PJ, Hazlerigg DG: Ancestral TSH mechanism signals summer in a photoperiodic mammal. Curr Biol 2008, 18:1147–52.
  2. Dardente H, Wyse CA, Birnie MJ, Dupré SM, Loudon ASI, Lincoln GA, Hazlerigg DG: A molecular switch for photoperiod responsiveness in mammals. Curr Biol 2010, 20:2193–8.
  3. Sáenz de Miera C, Monecke S, Bartzen-Sprauer J, Laran-Chich M-P, Pévet P, Hazlerigg DG, Simonneaux V: A circannual clock drives expression of genes central for seasonal reproduction. Curr Biol 2014, 24:1500–6.
  4. Sáenz de Miera C, Hanon EA, Dardente H, Birnie M, Simonneaux V, Lincoln GA, Hazlerigg DG: Circannual variation in thyroid hormone deiodinases in a short-day breeder. J Neuroendocrinol 2013, 25:412–21.
  5. Sáenz de Miera C, Bothorel B, Jaeger C, Simonneaux V, Hazlerigg D: Maternal photoperiod programs hypothalamic thyroid status via the fetal pituitary gland. Proc Natl Acad Sci 2017, 114:8408–8413.
  6. Lorgen M, Casadei E, Król E, Douglas A, Birnie MJ, Ebbesson LOE, Nilsen TO, Jordan WC, Jørgensen EH, Dardente H, et al.: Functional Divergence of Type 2 Deiodinase Paralogs in the Atlantic Salmon. Curr Biol 2015, 25:936–941.


 

Selected papers
 

  1. Please see google scholar for a full list: https://scholar.google.no/citations?user=chuO0UIAAAAJ&hl=en&oi=ao
  2. Saenz de Miera C, Bothorel B, Jaeger C, Simonneaux V. and Hazlerigg D (2017). Maternal photoperiod programs hypothalamic thyroid status via the fetal pituitary gland. Proceedings of the National Academy of Sciences p.201702943.
  3. Lorgen M, Jorgensen EH, Jordan WC, Martin SA and Hazlerigg DG (2017). NFAT5 genes are part of the osmotic regulatory system in Atlantic salmon (Salmo salar). Marine genomics 31:25-31.
  4. Lorgen M, Casadei E, Król E, Douglas A, Birnie MJ, Ebbesson LOE, Nilsen TO, Jordan WC, Jørgensen EH, Dardente H, Hazlerigg DG (CA), Martin SAM (2015) Functional Divergence of Type 2 Deiodinase Paralogs in the Atlantic Salmon. Current Biology 25:936-941.
  5. Saenz de Miera C, Monecke S, Bartzen-Sprauer J, Laran-Chich MP, Pévet P, Hazlerigg DG, Simonneauz V (2014) A circannual clock drives expression of genes central for seasonal reproduction Current Biology 24: 1500-1506.
  6. Dardente H, Wyse CA, Dupre SM, Birnie MJ, Loudon ASIL, Lincoln GA, Hazlerigg DG (2010) A molecular switch for photoperiod responsiveness in mammals. Current Biology 20:2193-2198. http://f1000.com/prime/7720957
  7. Hanon EA, Routledge K, Dardente H, Masson-Pévet 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 22: 51-55.
  8. 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 20: 1252-1259.
  9. 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. http://f1000.com/prime/1123360
  10. 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.
  11. Lincoln GA, Clarke IJ, Hut RA, Hazlerigg DG (2006) Characterizing a mammalian circannual pacemaker. Science 314:1941-1944. http://f1000.com/prime/1064743

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