Model-Based Inference of Age Related Changes in Circadian Oscillators
The mammalian circadian clock synchronizes the physiology and metabolism of an organism to the external light-dark phase. This optimizes energy expenditure and allows anticipation of daily recurring events. Rhythms with a periodicity of about a day are generated by interlocked transcriptional feedback loops and can be measured, for instance, by mRNA accumulation experiments.
Previously, we investigated the behavior of the coupled circadian oscillator in mouse liver under different photoperiods and we were able to describe the flexibility of a small regulatory sub-network of the circadian oscillator in terms of a mathematical model based on non-linear differential equations.
However, during the establishment of our model, we realized that the age of the animal impacts some but not all parts of the circadian oscillator. The aim of the IPhD Project is to develop our model to identify the molecular processes involved in the liver circadian oscillator that change with age based on experimental data and to search for potential targets that would mitigate these changes when properly modified using drug treatments.
Keywords: Circadian Clock, Liver, Age, Mathematical Modelback