Clock control of inflammation in the lung

The circadian clock is a critical regulator of physiology and behaviour and its disruption leads to disease. Virtually all cells of the body are driven by circadian pacemakers, which are coordinated by a central light-entrained clock in the brain. Our recent studies have revealed a critical role for circadian clocks in immune regulation. 

Using the lung as a model, we have shown that pacemakers within innate immune cells and airway cells are essential in regulating the magnitude of immune and inflammatory responses to injury. We will now exploit this to define how a tissue clockwork coordinates responses to injury, and the role of time-based signalling between different cell types. We will discover how the circadian clock and glucocorticoid hormones work together to coordinate cellular defence mechanisms by deleting genes in specific cell types in transgenic mice. We can use novel drug-like molecules, which act on the clock to investigate how cellular timers modify immune function.  

Emerging evidence has shown that the clock drives changes in gene expression by modifying DNA and its associated proteins. We will study this as it offers an explanation of the strikingly selective nature of the clock effect on immune response.