A synthetic distributed genetic multi-bit counter

Abstract

A design for genetically-encoded counters is proposed via repressor-based circuits. An N -bit counter reads sequences of input pulses and displays the total number of pulses, modulo 2N . 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. The N -bit counter is then obtained by interconnecting (using diffusible chemicals) a set of N single-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 Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/468063v1_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@19a5330org.highwire.dtl.DTLVardef@cbb5c2org.highwire.dtl.DTLVardef@a0b5borg.highwire.dtl.DTLVardef@16f9d07_HPS_FORMAT_FIGEXP M_FIG C_FIG