Award details

Melatonin readout in mammals: from Coincidence to Amplitude

Reference	BB/C514558/1
Principal Investigator / Supervisor	Professor David Hazelrigg
Co-Investigators / Co-Supervisors
Institution	University of Aberdeen
Department	School of Medical Sciences
Funding type	Research
Value (£)	271,076
Status	Completed
Type	Research Grant
Start date	01/08/2005
End date	31/05/2009
Duration	46 months

Abstract

This project aims to provide basic understanding of the mechanisms through which mammals use day-length to synchronise annual physiological cycles (for example moulting or breeding). These phenomena all depend upon the response of the hypothalamo-pituitary axis to the pineal hormone melatonin. We have focussed on the pars tuberalis as a model tissue for studying melatonin action, since it is a uniquely well characterised melatonin target tissue. Our recent work indicates that the relative timing of dusk and dawn are relayed to the pars tuberalis by the start and end of the nightly melatonin signal, as peaks in Cry1 and Per1 expression, respectively. Since the protein products of these genes interact to control circadian gene expression, we hypothesise that changing day-length acts through melatonin by changing the molecular coincidence between these factors. We wish to explore the predictions from this hypothesis using simulation modelling based on the Leloup Goldbeter model for circadian oscillation in mammalian cells, and to determine whether one can predict the amplitude of circadian oscillation in the pars tuberalis based on changing Per-Cry coincidence (coincidence to amplitude). We then wish to establish siRNA technology to allow us to determine whether knock-down of clock genes abolishes downstream responses to changing melatonin signals in pars tuberalis cells.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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