Srivastava Rajkamal, Bagh Sangram
Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Block A/F, Sector-I, Bidhannagar, Kolkata700064, India.
Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai400094, India.
ACS Synth Biol. 2023 Jan 20;12(1):51-60. doi: 10.1021/acssynbio.2c00520. Epub 2022 Nov 16.
Reversible logic gates are the key components of reversible computing that map inputs and outputs in a certain one-to-one pattern so that the output signals can reveal the pattern of the input signals. One of the main research foci of reversible computing is the implementation of basic reversible gates by various modalities. Though true thermodynamic reversibility cannot be attained within living cells, the high energy efficiency of biological reactions inspires the implementation of reversible computation in living cells. The implementation of synthetic genetic circuits is mostly based on conventional irreversible computing, and the implementation of logical reversibility in living cells is rare. Here, we constructed a 3-input-3-output synthetic genetic reversible double Feynman logic gate with a population of genetically engineered cells. Instead of following hierarchical electronic design principles, we adapted the concept of artificial neural networks (ANN) and built a single-layer artificial network-type architecture with five different engineered bacteria, named bactoneurons. We used three extracellular chemicals as input signals and the expression of three fluorescence proteins as the output signals. The cellular devices, which combine the input chemical signals linearly and pass them through a nonlinear activation function and represent specific bactoneurons, were built by designing and creating small synthetic genetic networks inside . The weights of each of the inputs and biases of individual bactoneurons in the bacterial ANN were adjusted by optimizing the synthetic genetic networks. When arranging the five bactoneurons through an ANN-type architecture, the system generated a double Feynman gate function at the population level. To our knowledge, this is the first reversible double Feynman gate realization with living cells. This work may have significance in development of biocomputer technology, reversible computation, ANN wetware, and synthetic biology.
可逆逻辑门是可逆计算的关键组件,它以特定的一一对应模式映射输入和输出,以便输出信号能够揭示输入信号的模式。可逆计算的主要研究重点之一是通过各种方式实现基本的可逆门。尽管在活细胞内无法实现真正的热力学可逆性,但生物反应的高能效激发了在活细胞中实现可逆计算的想法。合成遗传电路的实现大多基于传统的不可逆计算,而在活细胞中实现逻辑可逆性的情况很少见。在这里,我们用一群基因工程细胞构建了一个三输入三输出的合成遗传可逆双费曼逻辑门。我们没有遵循分层电子设计原则,而是采用了人工神经网络(ANN)的概念,并构建了一个由五种不同工程细菌组成的单层人工网络型架构,我们称之为细菌神经元。我们使用三种细胞外化学物质作为输入信号,并将三种荧光蛋白的表达作为输出信号。通过在细胞内设计和创建小型合成遗传网络,构建了将输入化学信号线性组合并使其通过非线性激活函数的细胞装置,这些装置代表特定的细菌神经元。通过优化合成遗传网络来调整细菌人工神经网络中各个细菌神经元的每个输入的权重和偏差。当通过人工神经网络类型的架构排列这五种细菌神经元时,该系统在群体水平上产生了双费曼门功能。据我们所知,这是首次用活细胞实现可逆双费曼门。这项工作可能对生物计算机技术、可逆计算、人工神经网络硬件和合成生物学的发展具有重要意义。