Engineering orthogonal cell-cell communication pathways in bacteria
Dr Neil Dalchau
Microsoft Research, Cambridge
Intercellular signalling confers a variety of abilities on multicellular organisms, from relaying environmental information among different organs, to co-ordinating pattern formation for organ and tissue development. Some of the signalling components involved in shaping developmental processes have been elucidated in model organisms. This has enabled a greater focus on understanding general design principles that allow patterning from biochemistry. For example, there have been numerous attempts to determine when developmental patterns emerge from the Turing mechanism of pattern formation, which relies on two distinct signals, or from the conceptually simpler morphogen gradient mechanism, which relies on only one signal.
Recently, our group has been working with a team of synthetic biologists to attempt forward engineering of pattern formation in multicellular systems, specifically starting with E. coli as a chassis. In doing so, we are attempting to understand what is required of a cellular system to establish Turing patterns. One fundamental requirement is the ability of cells to perceive and respond orthogonally to two signals. We therefore sought to develop two orthogonal signalling channels in E. coli, based on the well-established quorum-sensing systems from gram-negative bacteria. We have used mathematical modelling to optimise our designs, and the models are parameterised with experimental measurements. The development of an accurately parameterised model is now allowing us to reason about pattern formation in engineered systems with two-signal communication, for which I will show preliminary results.