Paul Grant and members of Jim Haseloff’s group, in collaboration with Neil Dalchau and Andrew Phillips from Microsoft Research, Cambridge, have developed a framework for building the cellular interactions required for engineering multicellular systems. Grant, Dalchau, and colleagues combined signaling pathways from V. fischeri and P. aeruginosa in E. coli and built a mathematical model of crosstalk in the system in order to engineer independent signaling channels. By growing these engineered bacteria on membranes printed with hydrophobic grids that kept populations isolated, and imaging fluorescent protein outputs, the authors were able to create synthetic multicellular systems in which both the genetics and the geometry were controlled. This allowed for an intercellular feedback loop that resulted in initiation and propagation of a signal through spatially separated populations.
Grant PK, Dalchau N, Brown, JR, Federici F, Rudge TJ, Yordanov B, Patange O, Philips A, Haseloff J. (2016) Orthogonal intercellular signaling for programmed spatial behavior. Molecular Systems Biology.