Building Patterns

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Paul Grant, James Brown, Neil Dalchau, Judy Savitskaya, Andrew Phillips, Jim Haseloff

Department of Plant Sciences, United Kingdom

In 1952, Alan Turing proposed a model for the emergence of self-organizing patterns from a near-homogeneous field of cells. His work presented a possible mechanism by which the diffusion and reaction of chemical substances would, through positive and negative feedback, amplify random differences within the field of cells resulting in stable patterns across the field. There has been much contentious debate about the biological relevance of Turing’s theoretical model but now, sixty years after the publication of Turing’s seminal paper, synthetic biology gives us the tools and the conceptual framework to build genetic circuits from known parts to specifically test Turing’s ideas divorced from the complexity and historical contingency of naturally evolved systems. I am currently developing the parts and devices required for creating a Turing-patterning circuit in E. coli. A key requirement for such a circuit is the presence of two diffusing substances that Turing called morphogens. The obvious choice for morphogens are acyl homoserine lactones (AHLs). I have developed a two-channel receiver for 3-oxo-C6-homoserine lactone (C6) and 3-oxo-C12-homoserine lactone (C12) that minimizes crosstalk between the channels and can be used as a platform for patterning circuits. In order for patterning to occur, morphogens must diffuse at different rates. Initial diffusion experiments suggest that diffusion coefficients of C6 and C12 are not sufficiently different. I am therefore attempting to use polymers that selectively bind single AHLs to influence diffusion rates to create the necessary difference. Modelling provides an estimate of parameters (including ratio of diffusion coefficients) required for the system but even with careful characterization it is difficult to land a full circuit into the appropriate spot in parameter space to achieve patterning, I am therefore using a parallel construction and screening approach to arrive at a functional circuit.