Moškon Miha, Pušnik Žiga, Zimic Nikolaj, Mraz Miha
Faculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia.
Faculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia.
Comput Biol Med. 2021 Jan;128:104109. doi: 10.1016/j.compbiomed.2020.104109. Epub 2020 Nov 12.
Synthetic biology applications often require engineered computing structures, which can be programmed to process the information in a given way. However, programming of these structures usually requires significant amount of trial-and-error genetic engineering. This process is to some degree analogous to the design of application-specific integrated circuits (ASIC) in the domain of digital electronic circuits, which often require complex and time-consuming workflows to obtain a desired response. We describe a design of programmable biological circuits that can be configured without additional genetic engineering. Their configuration can be changed in vivo, i.e. during the execution of their biological program, simply with an introduction of programming inputs. These, e.g., increase the degradation rates of selected proteins that store the current configuration of the circuit. Programming can be thus performed in the field as in the case of field-programmable gate array (FPGA) circuits, which present an attractive alternative of ASICs in digital electronics. We describe a basic programmable unit, which we denote configurable (bio)logical block (CBLB) inspired by the architecture of configurable logic blocks (CLBs), basic functional units within the FPGA circuits. The design of a CBLB is based on distributed cellular computing modules, which makes its biological implementation easier to achieve. We establish a computational model of a CBLB and analyse its response with a given set of biologically feasible parameter values. Furthermore, we show that the proposed CBLB design exhibits correct behaviour for a vast range of kinetic parameter values, different population ratios, and as well preserves this response in stochastic simulations.
合成生物学应用通常需要工程化的计算结构，这些结构可以通过编程以特定方式处理信息。然而，对这些结构进行编程通常需要大量反复试验的基因工程操作。这个过程在某种程度上类似于数字电子电路领域中专用集成电路（ASIC）的设计，后者通常需要复杂且耗时的工作流程才能获得期望的响应。我们描述了一种无需额外基因工程即可配置的可编程生物电路设计。它们的配置可以在体内改变，即在其生物程序执行期间，只需引入编程输入即可。例如，这些输入可以提高存储电路当前配置的特定蛋白质的降解速率。这样一来，就可以像现场可编程门阵列（FPGA）电路那样在现场进行编程，FPGA电路在数字电子领域是ASIC的一种有吸引力的替代方案。我们描述了一个基本的可编程单元，我们将其称为可配置（生物）逻辑块（CBLB），它的灵感来自于FPGA电路中的基本功能单元——可配置逻辑块（CLB）的架构。CBLB的设计基于分布式细胞计算模块，这使得它在生物学上更容易实现。我们建立了CBLB的计算模型，并使用一组给定的生物学上可行的参数值分析其响应。此外，我们表明，所提出的CBLB设计在广泛的动力学参数值、不同的种群比例下都表现出正确的行为，并且在随机模拟中也能保持这种响应。
