Research Focus
The focus of the research programme is to investigate the role of circadian clock genes in generating long-term cycles in reproduction, appetite, fattening and other seasonal characteristics. We are also searching for novel timer genes based on the mechanisms of cellular aging.

Background to the Research
Biological clocks and calendars influence most aspects of physiology and behaviour. Their importance is all too obvious to those who suffer the severe symptoms of jet-lag or SAD. We now know that at the core of biological timing is a set of highly conserved genes - called clock genes - that generate intrinsic daily rhythms. Clock genes are rhythmically expressed in all cells allowing co-ordination of complex processes within cells and tissues, and between the different body organs where neural and hormonal signals provide for communication. There is a small area at the front of the brain closely linked to the eyes that acts as a central pacemaker and synchronises the internal clockwork to the Earthly day.  Jet-lag can be seen as a state of internal de-synchrony (chaos) and it takes several days of regular time cues, particularly from sunlight, to reset the normal rhythmicity. Interestingly, variability in the structure of clock genes determines whether you are a lark or an owl, or whether you are prone to seasonal depression and alcoholism. We also know that clock genes in melatonin-responsive tissues underpin responsiveness to daylength and allow the precise timing of transitions in seasonal physiology. The mechanisms are only just emerging but already the molecular revolution has transformed our understanding of chronobiology.

Recent Progress
We have made recent progress in three main areas. In long-term studies using our Soay sheep model we have characterised the cellular basis of a circannual pacemaker that governs seasonal prolactin secretion (1). This is the first evidence that such a pacemaker may be localised at a tissue level. We are generating a model of a circannual clock based on a two-cell, delayed-feedback system. Micro-array analysis is being used to search for novel timer genes in the stalk region of the pituitary gland. Other studies have demonstrated that changes in nocturnal melatonin production dictate daily patterns of clock gene expression in melatonin-target tissues (2-5). This may provide the mechanism that decodes photoperiod to drive seasonality. We have also produced evidence that changes in daylength affect the expression of appetite regulating peptide genes in the hypothalamus, part of a neural network that governs seasonal changes in voluntary food intake, energy metabolism and fattening (6).

Link to Edinburgh Chronobiology Group: http://chronobiology.mvm.ed.ac.uk

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