Synthetic analog computation in living cells

  title={Synthetic analog computation in living cells},
  author={Ramiz Daniel and Jacob R. Rubens and Rahul Sarpeshkar and Timothy Kuan-Ta Lu},
A central goal of synthetic biology is to achieve multi-signal integration and processing in living cells for diagnostic, therapeutic and biotechnology applications. [] Key Method Our circuits can be composed to implement higher-order functions that are well described by both intricate biochemical models and simple mathematical functions.

Noise Tolerance Analysis for Reliable Analog and Digital Computation in Living Cells

Both systems are challenging to operate with low protein levels and it is shown that analog systems should operate with a Hill coefficient smaller than 1 and digital systems should be buffered to overcome this challenge.

Synthetic mixed-signal computation in living cells

This work presents a framework for building comparator gene circuits to digitize analogue inputs based on different thresholds, and demonstrates that comparators can be predictably composed together to build band-pass filters, ternary logic systems and multi-level analogue-to-digital converters.

Synthetic Gene Circuits

In this review, some examples are presented of commonly used synthetic circuits, including oscillators, switches, memory devices, and circuits that perform digital and analog computation.

Analog synthetic biology

  • R. Sarpeshkar
  • Computer Science
    Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences
  • 2014
It is concluded that synthetic biology must use analog, collective analog, probabilistic and hybrid analog–digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets.

Synthetic biology: insights into biological computation.

Digital computation can now be engineered and implemented in biological systems and can lead to new therapeutic approaches, as well as new and efficient ways to produce complex molecules such as antibiotics, bioplastics or biofuels.

Complex cellular logic computation using ribocomputing devices

It is demonstrated that ribocomputing devices in Escherichia coli can evaluate two-input logic with a dynamic range up to 900-fold and scale them to four-input AND, six-input OR, and a complex 12-input expression.

Synthetic biological circuits for continuous signal processing

This thesis describes the development of synthetic biological circuits that enable robust continuous signal processing and posit that the computational architecture demonstrated herein will enable novel applications for the field of synthetic biology.

Engineering of Gene Circuits for Cellular Computation

The current states of artificial gene circuits that perform digital and analog computation have been described.

Ribocomputing devices for sophisticated in vivo logic computation

It is demonstrated how toehold switches can be incorporated into decision-making RNA networks termed ribocomputing devices to rapidly evaluate complex logic in living cells.

A Synthetic Microbial Operational Amplifier

This work shows how to create a synthetic 3-stage inducer-input operational amplifier with a differential transcription-factor stage, a CRISPR-based push-pull stage, and an enzymatic output stage with just 5 proteins including dCas9.



Programmable single-cell mammalian biocomputers

This work has designed a set of synthetic transcription–translation control devices that could be rewired in a plug-and-play manner and shows that these combinatorial circuits integrated a two-molecule input and performed digital computations with NOT, AND, NAND and N-IMPLY expression logic in single mammalian cells.

Robust multicellular computing using genetically encoded NOR gates and chemical ‘wires’

This work helps elucidate the design rules by which simple logic can be harnessed to produce diverse and complex calculations by rewiring communication between cells.

A synthetic oscillatory network of transcriptional regulators

This work used three transcriptional repressor systems that are not part of any natural biological clock to build an oscillating network, termed the repressilator, in Escherichia coli, which periodically induces the synthesis of green fluorescent protein as a readout of its state in individual cells.

Higher-Order Cellular Information Processing with Synthetic RNA Devices

This work developed a general approach for assembling RNA devices that can execute higher-order cellular information processing operations from standard components that can function as logic gates and signal filters, and exhibit cooperativity.

Programmed population control by cell–cell communication and regulated killing

This work has built and characterized a ‘population control’ circuit that autonomously regulates the density of an Escherichia coli population and incorporates a mechanism for programmed death in response to changes in the environment.

Synchronizing genetic relaxation oscillators by intercell signaling

The ability to design and construct synthetic gene regulatory networks offers the prospect of studying issues related to cellular function in a simplified context; such networks also have many

Scaling Up Digital Circuit Computation with DNA Strand Displacement Cascades

This work experimentally demonstrated several digital logic circuits, culminating in a four-bit square-root circuit that comprises 130 DNA strands, which enables fast and reliable function in large circuits with roughly constant switching time and linear signal propagation delays.

Next-Generation Synthetic Gene Networks

As these challenges are addressed, synthetic biologists will be able to construct useful next-generation synthetic gene networks with real-world applications in medicine, biotechnology, bioremediation and bioenergy.

Analog transistor models of bacterial genetic circuits

It is shown that compact analog current-mode circuits are effective at quantitatively modeling the behavior of genetic circuits and can provide efficient conceptual, modeling, and simulation tools for the design and analysis of circuits in synthetic and systems biology.