Synthetic Morphogenesis

Synthetic morphogenesis is the endeavour to create bioogical form by engineering artificial genetic constructs into naive cells to ‘program’ them to create form. Typically, these modules are designed to be responsive to external signals so that the morphogenetic mechanisms can be under the control of experimenters, or even of other engineered cells.

Some years ago, one of the CyGenTiG investigators led a project that built a library of morphogenetic modules, which conferred drug-controlled morphogenetic behaviours on human cells. These behaviours included cell proliferation, elective cell death, cell fusion, cell locomotion and cell adhesion [1].

The same group has also designed and built synthetic biological modules that generate patterns, such as the one in the figure below [2].

They have also coupled this pattern formation to one simple form of morphogenesis – elective cell death – so that the engineered ’tissue’ first organizes itself into a pattern and then one pattern element dies to leave a ‘seive’ (a sheet with holes). This is a simple example of morphogenesis, but it is arguably t the first ever achievement of synthetic patterning followed by synthetic morphogenesis [3].

So far, our synthetic morphogenesis has been controlled by drugs, which by their nature reach all cells at once. The use of light as an external signal will allos us to ‘talk to’ specific cells.

References:

1. Cachat E, Liu W, Hohenstein P, Davies JA. (2014) A library of mammalian effector modules for synthetic morphology. J Biol Eng. 2014 Nov 19;8(1):26. doi: 10.1186/1754-1611-8-26..

2. Cachat E, Liu W, Martin KC, Yuan X, Yin H, Hohenstein P, Davies JA (2016) 2- and 3-dimensional synthetic de novo large-scale patterning by mammalian cells through phase separation. Scientific Reports 6:20664. doi: 10.1038/srep20664. (Available from here).

3. Cachat E, Liu W, Davies JA (2017) Synthetic self-patterning and morphogenesis in mammalian cells: a proof-of-concept step towards the goal of synthetic tissue development. IET Engineering Biology doi: 10.1049/enb.2017.0013

4. Davies JA. (2008) Synthetic morphology: prospects for engineered, self-constructing anatomies. J Anat. 2008 Jun;212(6):707-19. doi: 10.1111/j.1469-7580.2008.00896.x.