Akhilesh B. Reddy
Wellcome Trust Senior Fellow in Clinical Sciences
Department of Clinical Neurosciences
My laboratory is interested in circadian rhythms, which are daily cycles of physiology and behaviour that persist when organisms are isolated from the outside world. They represent a fundamental biological mechanism, and are present at all levels of life, from bacteria through to humans. They allow us 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 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 butother, 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 morbidity. 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.
Rey G, Reddy AB. (2013). Connecting cellular metabolism to circadian clocks. Trends Cell Biol, 2013 Feb 4. doi:pii: S0962-8924(13)00005-6. 10.1016/j.tcb.2013.01.003. [Epub ahead of print]. PMID: 23391694.
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. Proc Natl Acad Sci U S A. 2013 Jan 7. [Epub ahead of print]. PMID:23297224.
Olmedo M, O'Neill JS, Edgar RS, Valekunja UK, Reddy AB, Merrow M. (2012). Circadian regulation of olfaction and an evolutionarily conserved, nontranscriptional marker in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20479-84. doi: 10.1073/pnas.1211705109. Epub 2012 Nov 26. PMID: 23185015.
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. PMID: 22622569. PMCID: PMC3398137.
Reddy AB, O'Neil JS. (2011). Metaclocks. EMBO Rep, 12(7):612. doi: 10.1038/embor. 2011.123. PMID: 21720447. PMCID: PMC3128962.
O'Neil JS, Reddy AB. (2011). Circadian clocks in human red blood cells. Nature, 469:498-503. PMID: 21270888. PMCID: PMC3040566.
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. PMID: 21270895. PMCID: PMC3040569.
Maywood ES, Fraenkel E, McAllister CJ, Wood N, Reddy AB, Hastings MH, Morton AJ. (2010). Disruption of peripheral circadian timekeeping in a mouse model of Huntingdon's disease and its restoration by temporally scheduled feeding. J Neurosci, 30(30):10199-204. PMID: 20668203.
Reddy AB, O'Neill JS. (2010). Healthy clocks, healthy body, healthy mind.
Trends Cell Biol, 20(1):36-44. PMID: 19926479. PMCID: PMC2808409.
Deery MJ, Maywood ES, Chesham JE, Sládek M, Karp NA, Green EW, Charles PD, Reddy AB, Kyriacou CP, Lilley KS, Hastings MH. (2009). Proteomic analysis reveals the role of synaptic vesicle cycling in sustaining the suprachiasmatic circadian clock. Curr Biol, 19(23):2031-6. PMID: 19913422.