Multiscale Modelling of Signalling Microdomains

A key role of cells is to translate external signals into appropriate cellular responses. For example, when cells that line blood vessels experience weak stimulation, they initiate the expression of certain genes, while for strong stimuli, they begin to move. How cells accomplish such diverse responses is still an open question. What has transpired, though, is that so called microdomains are vital for cellular decision-making.

Microdomains are small parts of a cell where molecular mediators and switches are concentrated in close proximity. This is advantageous since cell signalling intrinsically relies on molecules interacting, and if they are close to each other, chances are higher that signal transduction is successful. In many cases, these signalling pathways rely on small molecules that diffuse through the microdomain and hence can carry information from one molecular partner to the next. To appreciate the full potential of the signalling micordomains, it is crucial to have a comprehensive understanding of the dynamics of these diffusible messengers.

In this project, we will use a combination of semi-analytical and numerical techniques to develop three dimensional models of signalling microdomains. In particular, we will investigate how the intracellular calcium concentration changes in space and time within microdomains, and how these changes affect signal transduction. Gaining deeper insights into microdomains is key for understanding for understanding healthy physiology such as fertilisation and muscle contraction as well as diseases such as immunodeficiency and neurological disorders. The model will be informed by experiments conducted at Oxford and Penn State University.