A fire-diffuse-fire framework for the functional organisation of cellular calcium signals

This work will establish a theoretical underpinning for how cells shape calcium signals in space, time and amplitude using components from a universal signalling toolkit. By considering the combined role of space, noise and heterogeneity in generating the variety of observed calcium signals we will be able to explore the mechanisms which allow a simple ion such as Ca++ to play such a pivotal role in cell biology.The need to make links to experiments forces one to look for cell models that incorporate both the discrete nature of calcium stores and the stochastic nature of calcium release. Work by Coombes on calcium waves in fire-diffuse-fire (FDF) models has focused on the former aspect and has recently been extended to cover the stochastic nature of calcium release. FDF models use a threshold process to mimic the nonlinear properties of Ca++ channels. The stochastic nature of release is incorporated via the introduction of threshold noise. This leads to a model with simple probabilistic update rules for the release of calcium from internal stores. This framework will be extended to include further important aspects of cell physiology known to play an important role in the generation of calcium signals. The development of these mathematical components will be guided by experiments being performed by Bootman and colleagues within the molecular signalling group at the Babraham Institute in Cambridge.