摘要：SummaryA design for genetically encoded counters is proposed via repressor-based circuits. AnN-bit counter reads sequences of input pulses and displays the total number of pulses, modulo2N. The design is based on distributed computation with specialized cell types allocated to specific tasks. This allows scalability and bypasses constraints on the maximal number of circuit genes per cell due to toxicity or failures due to resource limitations. The design starts with a single-bit counter. TheN-bit counter is then obtained by interconnecting (using diffusible chemicals) a set ofNsingle-bit counters and connector modules. An optimization framework is used to determine appropriate gate parameters and to compute bounds on admissible pulse widths and relaxation (inter-pulse) times, as well as to guide the construction of novel gates. This work can be viewed as a step toward obtaining circuits that are capable of finite automaton computation in analogy to digital central processing units.Graphical abstractDisplay OmittedHighlights•A single-bit counter is designed for a repressor-based genetic circuit•A scalable multi-bit counter is enabled by distributing the design across cells•A computational optimization framework is proposed to guide the designMathematical biosciences; Systems biology; Synthetic biology
