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Modelling: Big Data and Society Conference
A new PhD student publication
Dr. Michael Cohen
During his PhD, Michael investigated the phenomenon of patterning by cell-to-cell communication (Supervisors: Dr. Buzz Baum and Dr. Mark Miodownik). In a brief description of his research he tells us that:
"My research is on how patterns of differentiated cells are able form in developing multicellular organisms in a robust way. After conducting a fairly abstract study into this problem using cellular automata techniques derived from computer science my research has focused on a problem involving the spacing of microchaete bristles in drosophila flies. This patterning process has been attributed to lateral inhibition produced by the interaction of the transmembrane signalling proteins Delta and Notch. My work has been to develop a computational model in which filopodia, observed in the basal layer of the epithelium, carry the Delta signalling protein, across multiple cell distances. "
Michael used a computational model to demonstrate the viability of long range signalling through a dynamic network of filopodia, observed in the basal layer of the epithelium. In-vivo experiments confirmed that when filopodia lengths are effected by mutations the pattern spacing reduces in accordance with the model.
In his work, the behaviour of simple asynchronous cellular automata was analysed. A set of rules were identified whose emergent behaviour was similar to the lateral inhibition patterning process established by the Delta-Notch signalling system. Among these rules a particular subset were found to produce patterns that adjust their spacing, over the course of their development, towards a more ordered and densely packed state. A re-examination of the Delta-Notch signalling model revealed that this type of packing optimisation could take place with either dynamic filopodial signalling, or as an alternative, transient Delta signalling at each cell. Under certain parameter regimes the patterns become more densely packed over time, whilst maintaining a minimum zone of inhibition around each Delta expressing cell. Michael also used the asynchronous CA to demonstrate how stripes can be formed by cell-to-cell signalling and optimised, under certain conditions, so that they align in a single direction. He presented this as a possible novel alternative to the reaction-diffusion mechanism that is commonly used to model the patterning of spots and stripes.
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