Clock control of inflammation in the lung.
Description: The circadian clock is a critical regulator of physiology and behavior, and its disruption leads to disease. Virtually all cells of the body are driven by circadian pacemakers, which are co-ordinated by a central light-entrained clock in the brain. Our recent studies reveal 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 inflamma tory responses to injury. We will now exploit this to define how a tissue clockwork co-ordinates responses to injury, and the role of time-based signaling between different cell-types. Using transgenic mice to delete genes in specific cell types, we will discover how the circadian clock and glucocorticoid hormones work together to co- ordinate cellular defence mechanisms. We can use novel drug-like molecules, which act on the clock to investigate how cellular timers modify immune function. Fi nally, emerging evidence reveals 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.
Funder: Wellcome Trust
Amount:
Funding type: research
Funder scheme: Investigator Award in Science
Start date: 2016-07-01
End date: 2022-12-31
Investigator: Prof Andrew S I Loudon
Institution: University of Manchester
Funded outputs count: 85
Funder award ID: 107851/Z/15/Z
OpenAlex ID: G5043817205