[3S00m] 01. ASBA - Part 7

11:00 AM - 11:15 AM JST(2:00 AM - 2:15 AM UTC)

[3ASBA-06] Cell-Free and Cell-Based Platforms for Engineering Sense-Compute-Respond Biological Systems

○Jeong Wook Lee¹ (1. Pohang University of Science and Technology (POSTECH) (Korea))

Keywords:

sense-compute-respond,genetic circuits,cell-free biosensing,programmable biological systems

A defining challenge in synthetic biology is the construction of biological systems that autonomously sense molecular inputs, process information through defined logic, and generate programmed outputs. Here, we describe our progress toward this sense-compute-respond paradigm using complementary cell-free and cell-based approaches. In cell-free systems, we established a one-pot isothermal diagnostic platform in which target RNA recognition through probe hybridization and ligation gates T7 polymerase-driven transcription of a fluorescent RNA aptamer. This architecture implements binary decision-making at the molecular level: signal production is licensed only upon successful target detection. The platform was further adapted for single-nucleotide polymorphism discrimination by placing variant bases at the ligation junction, leveraging differential ligation efficiency as a sequence-resolution mechanism. In living cells, we developed a genetic circuit design framework that accommodates an expanded repertoire of logic operations and functions across multiple microbial hosts. Coupling transcription factor-based biosensors with these engineered circuits enables the assembly of cellular sense-compute-respond systems, in which small-molecule and metabolite sensing feeds into multi-layered signal processing and programmable biological actuation. This allows sustained and autonomous operation in complex biological environments, supporting decision-making beyond simple binary logic. These parallel efforts across cell-free and cell-based platforms provide a modular and scalable toolkit for programming biological systems that sense, decide, and act.