Scientific Philosophy
Our research is derived from the ethological approach handed down by the Nobel Laureate, Nikolaas Tinbergen (see here). The group's experimental reasoning is based on 'strong inference' outlined by Jon Platt (Science 1964 146 347-353) and uses 'multiple working hypotheses' highlighted by William Chamberlain (Science 1965 148 754-759). The main study models are seasonal organisms for two reasons: to expand our understanding on the basic mechanisms that time annual oscillations across (in)vertebrates and 2) to take advantage of the robust and predictable variation in organismal physiology, immunology and behaviour to improve our understanding of animal health & welfare, including humans.
Our research has received major funding from UK (Leverhulme Trust, BBSRC, Wellcome Trust) and Canadian (NSERC) councils. We have also benefited from the generous support from National Societies such as the British Society for Neuroendocrinology, Society for Reproduction and Fertility and the Royal Society of Edinburgh.
Rhythmic Epigenetics
Epigenetic modifications are generally associated
with permanent changes in DNA methylation, chromatin
structure etc. Our research has shown that these
epigenetic modifications can be reversed; and in many
cases exhibit rhythmic oscillations. The first study to
suggest that DNA methylation showed robust reversible
changes used our Siberian hamster (Phodopus sungorus).
We identified that the proximal promoter for the thyroid
hormone enzyme - deiodinase type III (dio3) - was associated with seasonal rhythms in reproductive physiology (PNAS 110 16651-16656). We have since expanded our research to reveal that the enzymes DNA methyltransferase 3a/b are highly dynamic and exhibit oscillations across multiple time scales and tissues/cell-type (Trends Genetics 34 90-100).
Light Detection by the Brain
In the vast majority of non-mammalian vertebrates, light is detected by extra-retinal photoreceptors (Trends Endo. Metab. 30 39-53). For a hundred years we have known that vertebrates have photoreceptors in the brainwhich control non-visual processes, most notably seasonality. These extra-retinal photoreceptors are critical for timing a range of physiological and behavioural traits. In birds, photoreceptors located in the hypothalamus are critical for the regulation of seasonal rhythms in reproductive physiology.
But despite many efforts the nature of the opsin(s) involved
has remained elusive. The current candidates for light detection
in birds includes: neuropsin (Eur J Neurosci 36 2859-2865)
and VA opsin (Curr Biol 19 1396-1402). In collaboration with
Simone Meddle and Ian Dunn, we are working to uncover
the functional significance of multiple extra-retinal
photoreceptors using Japanese quail (Coturnix Japonica).
Mechanisms of Seasonal Biology
The focus of the laboratory has been to sequence and annotate the Siberian hamster
genome and expand our molecular tools in non-traditional animal models. Recent work
seeks to take advantage of developments in CRISPR/Cas9 methods, as genome editing
is a powerful tool to establish gene-function relations. Current work in the laboratory
includes an investigation into hypothalamic plasticity in microRNA, in particular mir133b
and mir212. We have discovered that these microRNA show robust plasticity that are
predictive of reproductive and metabolic physiology and behaviour. Using cell cultures,
our group has found that these microRNAs regulate key neuropeptides and enzymes
previously implicated in timing feeding and body weight plasticity. These data are yielding
novel insights into an alternative mechanism for the neuroendocrine control of well-
established homeostatic circuits; and instead indicate long-term rheostatic processes are
involved. Moreover, we have established collaborative work with Domingo Tortonese
(Uni. Bristol) and David Bates (Uni. Nottingham) to investigate the role of hypothalamic angiogenesis for timing seasonal rhythms in hamsters. The research aims are an extension of our work that has identified brain angiogenesis inhibitor plasticity as a local mechanism that regulates the availability of nutrients and provides long-term rheostatic regulation of diverse physiological and behaviour traits (i.e. hibernation).
