Pharmacological and Genetic Dissection of the Cell-Autonomous Circadian Clock in Mammalian Cells
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Circadian rhythms are cell-intrinsic phenomena that permeate every level of biological scale, and thereby impact upon myriad aspects of human health and disease. The essential nature of cellular timekeeping remains an elusive yet critical objective for biomedical research.
Recent data suggests that, whilst essential to daily rhythms in behaviour and physiology, cycling clock gene expression is not sufficient to account for the circadian timekeeping within individual mammalian cells. This project will work within a small group to identify the key molecular mechanisms that sustain cellular circadian rhythms, and how this timing information is integrated within cellular signalling and metabolic networks in vitro and in vivo.
A successful candidate will be highly motivated, with a strong background in molecular and cellular biochemistry. Prior experience with circadian research and/or programming would be desirable.
Feeney KA et al. (2016)
Daily magnesium fluxes regulate cellular timekeeping and energy balance.
Nature. Apr 21;532(7599):375-9.
O'Neill, J.S. et al. (2013)
Cellular mechanisms of circadian pacemaking: beyond transcriptional loops.
Handb Exp Pharmacol. (217):67-103.
O'Neill, J.S. et al. (2011)
Circadian rhythms persist without transcription in a eukaryote.
O'Neill, J.S. and Reddy, A.B. (2011)
Circadian clocks in human red blood cells.
O'Neill, J.S. et al. (2008)
cAMP-dependent signaling as a core component of the mammalian circadian pacemaker