Synthetic Morphology: Using synthetic biology modules to engineer model tissues

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Kim Martin, Elise Cachat, Weijia Liu and Jamie A. Davies

University of Edinburgh, United Kingdom

Synthetic morphology is the application of synthetic biology approaches to build anatomical systems. Well-characterised genetic circuits have previously been designed and implemented in both pro- and eukaryotic cells. Such synthetic circuits, in combination with carefully-chosen ‘morphogenetic effectors’, can be designed to integrate external signals and output phenotype – providing a powerful tool-kit for engineering cellular behaviour and morphogenesis. Epithelial tubulogenesis is crucial to higher eumetazoa in defining epithelial organs such as the kidney. Despite its key role in development, the mechanisms underlying tubule outgrowth are still poorly understood. The physicist Richard Feynmann is quoted as having said: “What I cannot create, I do not understand”; synthetic morphology opens the door to understanding systems by a ‘constructionist’ rather than ‘reductionist’ approach – learning by building. Modularity and reusability of genetic ‘parts’ (dubbed ‘BioBricks’ in some circles) is one of the fundamental principles of synthetic biology. We are assembling a library of morphogenetic effectors for use in mammalian cells, and are in the process of testing potential effectors (‘parts’) with the aim of placing them under the control of synthetic circuits to drive tubule formation in Madin-Darby Canine Kidney (MDCK) strain II cells. This constructive approach will allow us to determine the roles and necessity of the signalling pathways and downstream effectors that have already been identified as important in tubule outgrowth more precisely; an approach which will complement and add to the existing body of work. For more information, please see the synthetic morphology platform paper: Davies, J. A. (2008). Synthetic morphology: prospects for engineered, self-constructing anatomies. Journal of Anatomy, 212(6), 707-19. We gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC) and the Anatomical Society.