Building a synthetic cell patterning mechanism to test a biological model

This project aims to extend the scope of synthetic biology, an emerging discipline that applies engineering approaches to life to create new, designed cell behaviours and engineered biological devices. Specifically, our aim is to engineer a genetic machine that causes cultures of cells to create spontaneous patterns, a technology that will both teach us about natural patterning and will also lay the foundations for really advanced tissue engineering.

The genetic machine we are building will use an architecture developed in theoretical terms in the 1950s, by the great mathematician Alan Turing. It would not have been possible to build the system then, long before genetic engineering was invented, but it is now. The system is conceptually very simple. The engineered cells will produce two molecules – an Activator, which travels away from the cell that produces it only slowly, and an Inhibitor, which spreads rapidly. Both molecules will be fluorescent, glowing different colours, to allow their presence to be detected. The Activator will drive, in a dose-dependent manner, its own production and the production of the Inhibitor: the Inhibitor will inhibit this effect of the Activator. A system like this has a natural instability: cells that produce lots of Activator will maintain their own activation but, through their high production of Inhibitor that spreads away well, they will also prevent the activation of neighbours. Depending on conditions, this system should cause the cells to produce spots, stripes, swirls or travelling waves of activation.

simulation jpg

Computer simulation of a pattern made by the system that will be built in real cells in this project. The left panel shows the pattern of Activator concentration while the right panel shows Inhibitor. In both cases, red indicates highest levels, and green, turquoise, blue and black progressively lover levels.

The idea has been explored extensively by computer simulation but building it in real cells would both generate the first synthetic spontaneous living pattern generator, and prove the feasibility of Turing's original idea about how natural patterns (for example, zebra stripes and leopard spots) arise.

Professor Jamie Davies
University of Edinburgh

Jamie was awarded a Research Project Grant in June 2012.