Modelling the cell-autonomous lung circadian clock #

Matthew Leak

10:50 Wednesday in 2Q42.

Part of the Mathematical modelling of sleep and circadian rhythms: from molecular mechanisms to policy session.

Abstract #

The timing of a large number of biological processes in mammals is determined by endogenous circadian clocks, produced by molecular transcriptional and translational feedback loops. Although the fundamental clock mechanism is the same across the entire organism, each tissue has a different clock, with circadian species have tissue-specific phases that determine biological timing. Consequently, to model circadian rhythms accurately, it is necessary to have tissue-specific models that reproduce known phase differences between molecular species. Although there have been a number of models put forward for circadian rhythms in the past, there is a scarcity of published lung models, and none that are sufficiently detailed to be able to recapitulate known phenotypes. An accurate lung model that includes all known interactions of the core clock will have application in studying diseases that attack the lungs, as well as developing chronotherapeutic strategies for drug administration to maximise treatment efficacy. In this talk I will discuss our work on developing a detailed and up-to-date lung clock model, utilising recent ChIP-Seq data to identify the regulatory network of the core clock.