This article belongs to the Special Issue Synthetic Biology: From Living Computers to Terraformation. ; We present a scheme for implementing a version of task switching in engineered bacteria, based on the manipulation of plasmid copy numbers. Our method allows for the embedding of multiple computations in a cellular population, whilst minimising resource usage inefficiency. We describe the results of computational simulations of our model, and discuss the potential for future work in this area. ; The work of A.G.-M. is supported by the SynBio3D (UK-EPSRC-EP/R019002/1) project of the UK Engineering and Physical Sciences Research Council and the BioRoboost (EU-H2020-BIOTEC-820699) Contract of the European Union. The work of AR-P is supported by the Spanish TIN2016-81079-R, (MINECO AEI/FEDER, EU) and Madrid Gov. project B2017/BMD-3691, InGEMICS-CM (FSE/FEDER, EU). Work in FdlC laboratory was financed by grant BFU2017-86378-P from the Ministry of Science and Technology (Spain). ; Peer reviewed
We present a scheme for implementing a version of task switching in engineered bacteria, based on the manipulation of plasmid copy numbers. Our method allows for the embedding of multiple computations in a cellular population, whilst minimising resource usage inefficiency. We describe the results of computational simulations of our model, and discuss the potential for future work in this area. ; The work of A.G.-M. is supported by the SynBio3D (UK-EPSRC-EP/R019002/1) project of the UK Engineering and Physical Sciences Research Council and the BioRoboost (EU-H2020-BIOTEC-820699) Contract of the European Union. The work of AR-P is supported by the Spanish TIN2016-81079-R, (MINECO AEI/FEDER, EU) and Madrid Gov. project B2017/BMD-3691, InGEMICS-CM (FSE/FEDER, EU). Work in FdlC laboratory was financed by grant BFU2017-86378-P from the Ministry of Science and Technology (Spain).
As synthetic biology moves away from trial and error and embraces more formal processes, workflows have emerged that cover the roadmap from conceptualization of a genetic device to its construction and measurement. This latter aspect (i.e., characterization and measurement of synthetic genetic constructs) has received relatively little attention to date, but it is crucial for their outcome. An end-to-end use case for engineering a simple synthetic device is presented, which is supported by information standards and computational methods and focuses on such characterization/measurement. This workflow captures the main stages of genetic device design and description and offers standardized tools for both population-based measurement and single-cell analysis. To this end, three separate aspects are addressed. First, the specific vector features are discussed. Although device/circuit design has been successfully automated, important structural information is usually overlooked, as in the case of plasmid vectors. The use of the Standard European Vector Architecture (SEVA) is advocated for selecting the optimal carrier of a design and its thorough description in order to unequivocally correlate digital definitions and molecular devices. A digital version of this plasmid format was developed with the Synthetic Biology Open Language (SBOL) along with a software tool that allows users to embed genetic parts in vector cargoes. This enables annotation of a mathematical model of the device's kinetic reactions formatted with the Systems Biology Markup Language (SBML). From that point onward, the experimental results and their in silico counterparts proceed alongside, with constant feedback to preserve consistency between them. A second aspect involves a framework for the calibration of fluorescence-based measurements. One of the most challenging endeavors in standardization, metrology, is tackled by reinterpreting the experimental output in light of simulation results, allowing us to turn arbitrary fluorescence units into relative measurements. Finally, integration of single-cell methods into a framework for multicellular simulation and measurement is addressed, allowing standardized inspection of the interplay between the carrier chassis and the culture conditions. ; This work was supported by the CAMBIOS Project of the Spanish Ministry of Economy and Competitiveness; the EVOPROG, ARISYS, and EMPOWERPUTIDA Contracts from the European Union; and the PROMT Project of the Madrid Regional Government to V.d.L. ; Peer reviewed
Synthetic biology uses living cells as the substrate for performing human-defined computations. Many current implementations of cellular computing are based on the "genetic circuit" metaphor, an approximation of the operation of silicon-based computers. Although this conceptual mapping has been relatively successful, we argue that it fundamentally limits the types of computation that may be engineered inside the cell, and fails to exploit the rich and diverse functionality available in natural living systems. We propose the notion of "cellular supremacy" to focus attention on domains in which biocomputing might offer superior performance over traditional computers. We consider potential pathways toward cellular supremacy, and suggest application areas in which it may be found. ; A.G.-M. was supported by the SynBio3D project of the UK Engineering and Physical Sciences Research Council (EP/R019002/1) and the European CSA on biological standardization BIOROBOOST (EU grant number 820699). T.E.G. was supported by a Royal Society University Research Fellowship (grant UF160357) and BrisSynBio, a BBSRC/ EPSRC Synthetic Biology Research Centre (grant BB/L01386X/1). P.Z. was supported by the EPSRC Portabolomics project (grant EP/N031962/1). P.C. was supported by SynBioChem, a BBSRC/EPSRC Centre for Synthetic Biology of Fine and Specialty Chemicals (grant BB/M017702/1) and the ShikiFactory100 project of the European Union's Horizon 2020 research and innovation programme under grant agreement 814408.
