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.

Human red blood cells have a biological
clock even though they have no nucleus.

Isolated mouse fibroblasts show
cycling gene activity over many days in vitro.

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 causes and consequences of cellular circadian timekeeping and how this biological clock communicates with other cellular systems. 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

  • Nathaniel Hoyle
  • Priya Crosby
  • Marrit Putker
  • Alessandra Stangherlin
  • David Tourigny
  • David Wong
  • Rachel Edgar