Year: 2022

EXPANDING REPERTOIRE. “To date, a number of synthetic gene circuits have been constructed to perform various digital logic functions and have demonstrated the great potential of using biological computational circuits to customize cell signalling.” https://lnkd.in/dsEUY4ZP View in LinkedIn

MODULAR GOAL. “However, most of these gene circuits are not modular (that is, they are limited by having to use specific inputs and outputs) or are not insulated from their host chassis (that is, they are limited by having to operate in a specific genetic background to avoid potential cross-talk or at the cost of affecting the host genetic machinery).” https://lnkd.in/dsEUY4ZP View in LinkedIn

BESPOKE APPLICATIONS. “These limitations prevent their reuse and rapid incorporation into larger biological systems to achieve more complex logic functions.” https://lnkd.in/dsEUY4ZP View in LinkedIn

IDEAL STRUCTURE. “Ideally, a genetic logic device should be modular and orthogonal to their host chassis to facilitate its reuse and reliability in different contexts.” https://lnkd.in/dsEUY4ZP View in LinkedIn

THE CHALLENGE. “Nevertheless, the effort in designing modular and orthogonal genetic devices is largely constrained by the fact that there are only a limited number of orthogonal regulatory components in the current toolbox of gene circuit engineering, such as transcription factor tetR, cI, luxR genes and their regulatory promoters.” https://lnkd.in/dsEUY4ZP View in LinkedIn

ENGINEERED CHASSIS. “Hence, a pressing need is to extend this limited parts list, for example, by exploiting and re-engineering the diverse, naturally evolved orthogonal biological control modules in many organisms.” https://lnkd.in/dsEUY4ZP View in LinkedIn

EXAMPLE. “A modular and orthogonal genetic AND gate was constructed in E. coli using a new strictly regulated orthogonal system from P. syringae. The hrpR/hrpS hetero-regulation of the σ54-dependent transcription allowed the AND gate to be tightly controlled with a robust near-digital logic behaviour.” https://lnkd.in/dsEUY4ZP View in LinkedIn

COMPLEX MODULARITY. “The device integrated two individual environmental signals through the two transcriptional inputs to generate one output response, accordingly, in the logic AND manner. The AND gate was shown to be modular by exchanging the inputs and output of the circuit while preserving the logic AND function.” https://lnkd.in/dsEUY4ZP View in LinkedIn

LEGO GENES. “A modular combinatorial logic NAND gate was generated by directly connecting the AND gate output to a NOT gate module. Because of modularity, the AND and NAND gates can be reconnected to different sensor inputs to integrate multiple environmental and cellular signals and thus be applied to identify a specific combinatorial condition, like the cancer microenvironment.” https://lnkd.in/dsEUY4ZP View in LinkedIn

VERIFIED. “The transcription-based AND gate was shown to be robust with functionality in a range of different tested contexts.” https://lnkd.in/dsEUY4ZP View in LinkedIn