1. J.P. Padmakumar, J. Sun 2, W. Cho 3, Y. Zhou, C. Krenz, Zhong Han W.Z, D. Densmore, E. D. Sontag, and C.A. Voigt. Partitioning of a 2-bit hash function across 66 communicating cells. Nature Chemical Biology, 20, 2024. [PDF] Keyword(s): synthetic biology, distributed computation, Boolean functions. Abstract:

   Powerful distributed computing can be achieved by communicating cells that individually perform simple operations. We have developed design software to divide a large genetic circuit across cells as well as the genetic parts to implement the subcircuits in their genomes. These tools were demonstrated using a 2-bit version of the MD5 hashing algorithm, an early predecessor to the cryptographic functions underlying cryptocurrency. One iteration requires 110 logic gates, which were partitioned across 66 strains of Escherichia coli, requiring the introduction of a total of 1.1 Mb of recombinant DNA into their genomes. The strains are individually experimentally verified to integrate their assigned input signals, process this information correctly, and propagate the result to the cell in the next layer. This work demonstrates the potential to obtain programmable control of multicellular biological processes.




2. T. Chen, M. A. Al-Radhawi, C.A. Voigt, and E.D. Sontag. A synthetic distributed genetic multi-bit counter. iScience, 24:103526, 2021. [PDF] Keyword(s): counters, synthetic biology, transcriptional networks, gene networks, boolean circuits, boolean gates, systems biology. 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 $2^N$. 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.

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