Integrated Calendar

Every cell in the body has its own molecular 24 hour clock, allowing it to coordinate its daily activities, just as we use a watch to organise our daily lives. This fact has become more and more important as we live in a "24/7 culture”, with transatlantic air travel and shift-work being part of normal life for an estimated 25% of Europeans. Desynchronizations that disrupt our daily clock, and thus our regular physiology, are now linked to diseases such as diabetes, obesity, neurodegeneration and cancer.

We have uncovered novel mechanisms about how the clock functions to maintain 24 hour time. Our work in red blood cells and marine algae has exposed the surprising and unanticipated role of redox (chemical) oscillations as key drivers in cellular timing. A family of proteins called the peroxiredoxins are a key readout of the clockwork, and their circadian oscillation is, remarkably, conserved in all phylogenetic domains of life, including Bacteria, Archaea and Eukaryotes. Thus, redox mechanisms are deeply embedded within the clockwork of multiple species, in stark contrast to the lack of evolutionary conservation of transcriptional components of the clockwork. Indeed, targeting redox oscillations using novel compounds directed towards peroxiredoxin proteins provides a new route to modifying 24 hour oscillations for potential health gains in multiple organ systems.

Metabolic and redox processes in cells are thus intimately linked to the clockwork, and in particular we have recently found that the redox-sensitive transcription factor NRF2 is an important communication route linking redox and transcriptional rhythms.