Multilevel Modelling of Morphogenesis

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The core research focuses on developmental processes through a unique style of multilevel-modelling. By integrating gene regulatory networks and biophysical properties of single cells, through cell deformation, motion and tissue level properties, we study emerging phenomena on the level of multiple cells, organs, as well as the development of whole organisms. To do so, we are coupling the Cellular Potts Model, a model formalism that is very powerful for describing the biophysics of cell dynamics, to gene regulations and metabolics. Mathematical and computational techniques are applied to study the behaviour that emerges from the model at different intermediate levels of organisation, as well as at the level of the whole organism. It provides a framework in which experimental findings related to metabolism and gene regulation can be linked to the observed development, from the cellular level to the level of the whole organism. The focus is towards developmental mechanisms in plants, but with a strong emphasis on the similarities and differences these exhibit to animal development, to overcome the strong segregation that prevails in scientific literature between plant and animal studies that obscures the identification of striking similarities and conserved core mechanisms. Integrated studies of developmental biology requires the cycling between modelling, imaging and experiments. We are developing methods to derive cell shape and time dynamics from (time series of) (3D) images, as well as ways to determine and correct for biases in imaging data, and to extend this by generating through the image analysis substrates for in silico studies. This strategy allows us to test proposed gene regulatory networks, transport mechanisms, etc, using computational techniques and realistic, experimentally measured cells shapes and tissue organisations. To finish the loop, the modelling insights are then used to further steer the experiments.

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