Introducing high-level modular design to synthetic bio-systems development

Despite the noticeable advancement in synthetic biology, developing novel biological systems can still be difficult. This partially stems from issues with optimising designs in an iterative manner, as there is a strong reliance on genetic engineering which is often a long and costly process. Additionally, aspects of biological designs can be difficult to re-use in new systems due to a lack of context-free characterisation data and incompatible assembly standards.

Presented here is a method for applying high-level modularisation to the development of biological systems, with the aim of alleviating the issues discussed above. This method allows designs to be split into functional modules, which provides numerous advantages. Some of these advantages include promoting the re-use of specific aspects from previous systems, and the ability to easily incorporate top-down design automation. Furthermore, each functional module can be expressed by separate cells which communicate via quorum sensing. This multicellularity can ease the implementation of designs by not requiring additional genetic engineering, reducing cellular burden, and introducing a new, easily accessible design space; cell ratios.

To validate this approach, a genetic biosensor has been split into three functional modules (a detector, a signal processor, and a reporter), as originally described by the Newcastle 2017 iGEM team. Each module is expressed in separate cells which have been characterised separately using a multifactorial Design of Experiments (DoE) approach to provide context-free characterisation data. A stochastic model has also been developed to investigate the cell-ratio design space and inform testing of the modular, multicellular biosensor.