SPEAKER:   Adam Stinchcombe, University of Toronto

ABSTRACT:  

In order to address questions related to shift-work, jet lag, and a variety of diseases, a detailed simulation of the circadian (24-hour) timekeeping mechanism is essential. The site of the master clock is the suprachiasmatic nucleus (SCN), which consists of 20,000 electrically and chemically coupled neurons. The molecular clock is a transcription-translation feedback loop within each neuron that is modelled by a system of 180 ordinary differential equations. On a faster timescale, the electrical activity of these neurons is driven by voltage-gated ion channels, internal calcium dynamics, and synaptic currents, which are described by a ten-variable ordinary differential equation. In this talk, I will discuss some of the details of our model, as well as the numerical challenges associated with solving this large and multi-scale differential equation. Through a combination of experiment, mathematical modeling, and simulation, we gain insight into mammalian circadian biology. In particular, I will show how the simulation revealed properties of the in-vivo SCN network connectivity, addressing a basic science question. Also, I will show how the simulation can be used to 'optimally' recover from jet lag.