Cellular rhythms, signalling and metabolic regulation
Circadian (approximately daily) rhythms are cell-autonomous oscillations that permeate every level of biology, and thereby impact upon many aspects of health and disease. In humans for example, our sleep/wake cycle has a clear circadian rhythm, as do numerous aspects of physiology and metabolism. Clock disruption, as occurs during shift work, has been strongly linked with conditions such metabolic syndrome, heart disease and various cancers. The molecular basis of cellular timekeeping remains an elusive yet critical objective for biomedical research.
Current evidence suggests that whilst cycles of nascent ‘clock gene’ expression are required for daily rhythms in behaviour and physiology, they are insufficient to explain circadian timekeeping at the cellular level. Our current research is focused on understanding the fundamental mechanisms of cellular circadian timekeeping and how this biological clock regulates other cellular systems, such as the actin cytoskeleton. To achieve these goals we employ a wide range of molecular biology, proteomic, metabolomic and biochemical techniques, supported by real-time fluorescent and bioluminescent reporters.
Currently we are particularly interested in metabolic and signaling processes with conserved roles in biological timekeeping. By understanding how the cellular clock evolved we can better grasp its function in human cells and tissues.
- Hoyle, N. P., Seinkmane, E., Putker, M., Feeney, K. A., Krogager, T. P., Chesham, J. E., Bray, L. K., Thomas, J. M., Dunn, K., Blaikley, J. & O'Neill, J. S. (2017)
Circadian actin dynamics drive rhythmic fibroblast mobilization during wound healing.
Science Translational Medicine, 8;9(415).
- Feeney K. A., Hansen L. L., Putker M., Olivares-Yañez C., Day J., Eades L. J., Larrondo L. F., Hoyle N. P., O'Neill J. S., van Ooijen G (2016)
Daily magnesium fluxes regulate cellular timekeeping and energy balance
Nature 532(7599): 375-379
- Causton, H.C., Feeney, K.A., Ziegler, C.A. and O'Neill, J.S. (2015)
Metabolic Cycles in Yeast Share Features Conserved among Circadian Rhythms.
Curr Biol. 25: 1056-1062
- O'Neill, J.S., van Ooijen, G., Dixon, L.E., Troein, C., Corellou, F., Bouget, F.Y., Reddy, A.B. and Millar, A.J. (2011)
Circadian rhythms persist without transcription in a eukaryote.
Nature 469: 554-558
- O'Neill, J.S. and Reddy, A.B. (2011)
Circadian clocks in human red blood cells.
Nature 469: 498-503
- Hastings, M.H., Maywood, E.S. and O'Neill, J.S. (2008)
Cellular circadian pacemaking and the role of cytosolic rhythms.
Curr Biol. 18: R805-R815
- Andrew Beale
- Nina Rzechorzek
- Estere Seinkmane
- Alessandra Stangherlin
- David Wong