Boolean logic gates are often considered the basic elements to construct more complex computational systems. When applying this approach to biocomputation in mammalian cells, a number of biological challenges, limit the level of achievable complexities when building multilayered networks. “We were always keeping an eye on the capability to overcome this long-lasting hurdle of expanding the computational capacity of mammalian cells,” says Mingqi Xie at Westlake University. Xie and colleagues Jiawei Shao, Lingyun Zhu, Hui Wang and others have developed a new strategy of biocomputation using tristate buffers.
A tristate buffer in electronics uses an upstream switch to control a downstream switch, with the downstream input determining the circuit output only when it is in the state in which it is plugged by the upstream switch. Following a similar idea, in mammalian cells, the researchers used two small molecules acting as the external input signals that control a gene circuit that consists of an upstream transcription-based switch and a downstream translation-based gene switch mediated by synthetic translation initiation factors. Connecting and expanding such core elements, gene networks that facilitate various multichannel input–output calculations can be constructed by a modular engineering rationale. This so called TriLoS (tristate-based logic synthesis) framework takes advantage of the similarity between its hierarchical structure and what is often observed in biological regulatory networks. It also benefits from the fact that, while tristate buffers in electronics typically have three types of output signal (0, 1 and unplugged Z), biological systems need only distinguish two output states (ON and OFF), notes Xie. “In fact, this approximation was probably a key factor for robust, resource-efficient and interference-free biocomputation.”
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