From genes to tissue surface tension

Project ID: 2531ad1544

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UCL Lead department: Laboratory for Molecular Cell Biology (LMCB)

Project Summary:

The surface tension of groups of cells is emerging as a key regulatory determinant of tissue architecture and collective cell decision making, in both development and disease. However, beyond phenomenological models, we do not understand the basic principles for how surface tension is regulated by cells to control emergent cellular behaviours. We now have a genetic window into understanding the emergence of surface tension in cell groups, using the group biology of the simple eukaryote, Dictyostelium. We have recently identified that subclones of the major laboratory isolates have cell aggregates that showing different liquid-like behaviours. These behaviours include simple clumps that look like flat domes, more elongated “sausage” clumps and hemispherical domes. These different structures indicate different surface tensions. We will sequence the genomes of these different strains, to identify the mutations that can modify the surface tension of the cell group. Mutations will then be reintroduced into cells, to explore their different group behaviours. We will explore the effects of the mutations with reference to the biological processes the affected genes are involved in, together with agent-based and continuum models that try to recapitulate the different group behaviours based on the physical changes predicted from the causative genes. This work will have broad implications for manipulating collective cell behaviour for in vitro tissue generation.