Biological Clocks & Sleep

Circadian (approx. 24 hour) rhythms are daily cycles of physiology and behaviour. They represent a fundamental biological mechanism, and are present at all levels of life, from bacteria through to humans. We need them in order to anticipate, and thus adapt to, the solar cycle of night and day. 

Although we now understand a great deal about some components of the clockwork, our recent work has implicated a significant contribution of non-transcriptional and post-translational processes to the time-keeping mechanism. In particular, we are interested in redox and metabolic oscillations that power the clockwork within single cells and tissues, such as those shown by peroxiredoxin proteins. 

In humans, the sleep-wake cycle is the most obvious circadian rhythm but other, more subtle, endocrine rhythms coordinate our body's physiology. Disruption of our circadian programming through old age, neurological disease, and even shift-work, is a growing cause of significant ill health. Of note, disorders of metabolism, as well as cancer, have now been closely linked to circadian dysfunction. 

We thus use a wide range of multi-disciplinary approaches, encompassing synthetic and systems biology, to deconstruct how clocks in the brain and in visceral tissues are able to control this vast array of physiological processes.

Selected publications

Reddy AB, Rey G. (2014) Metabolic and Nontranscriptional Circadian Clocks: Eukaryotes. Annu Rev Biochem.83:165-89 

Valekunja UK, Edgar RS, Oklejewicz M, van der Horst GT, O'Neill JS, Tamanini F, Turner DJ, Reddy AB. (2013). Histone methyltranserase MLL3 contributes to genome-scale circadian transcription. PNAS. 110(4):1554-9 

Edgar RS, Green EW, Zhao Y, Ooijen G, Olmedo M, Qin X, Xu Y, Pan M, Valekunja UK, Feeney KA, Maywood ES, Hastings MH, Baliga NS, Merrow M, Millar AJ, Johnson CH, Kyriacou CP, O'Neil JS, Reddy AB. (2012). Peroxiredoxins are conserved markers of circadian rhythms. Nature, 485(7399):459-64.  

O'Neil JS, Reddy AB. (2011). Circadian clocks in human red blood cells. Nature, 469:498-503. 

O'Neil JS, van Ooijen G, Dixon LE, Troein C, Corellou F, Bouget FY, Reddy AB*, Millar AJ*. (2011). Circadian rhythms persist without transcription in eukaryote. Nature, 469:554-558