John O’Neill

Cellular rhythms, signalling and metabolic regulation

oneillj@mrc-lmb.cam.ac.uk

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.

Cellular clocks drive daily rhythms of clock gene activity that persist for many days, in isolated skin cells for example

Wounds that happen during the active phase of the circadian cycle heal more rapidly because cells are quicker to migrate and repair the damage
Wounds that happen during the active phase of the circadian cycle heal more rapidly because cells are quicker to migrate and repair the damage (Hoyle et al 2017, Science Translational Medicine)

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.

Certain metabolic and signalling mechanisms have more ancient functions in
biological rhythms than do known ‘clock genes’.

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.

Selected Papers

Group Members

  • Priya Crosby
  • Alessandra Stangherlin
  • David Tourigny
  • David Wong
  • Estere Seinkmane