LEGO-inspired advances in life sciences drives customizable sensor technology

A research team, consisting of Professor Jongmin Kim, PhD candidates Jeongwon Kim, Minchae Seo, and Yelin Lim from the Department of Life Sciences at POSTECH, has developed an RNA-based sensor platform that can regulate gene expression in bacteria. Their findings were recently featured in the online edition of Advanced Science, a prominent international scientific journal.

The concept of managing obesity by boosting beneficial microorganisms in the body has recently gained attention from both the public and media. Probiotics, beneficial microorganisms typically present in the gut and other organs, aid in digesting food, absorbing nutrients, and producing essential vitamins such as vitamin B and K. Additionally, they play a crucial role in regulation of immune system and reduction of inflammation. This has led to the concept of "smart probiotics" where probiotics are combined with cutting-edge synthetic biological technologies such as biosensors and gene editing, representing an exciting frontier in healthcare.

The most critical aspect of "smart probiotics" technology lies in the “sensors.” Since biological systems function as intricate networks with precise interactions, it's essential to monitor changes in the intestinal environment in real time and control microbial activity accordingly. However, challenges including biocompatibility, accuracy, and sensitivity limit the types of components that can be used in these sensors, making technological development difficult.

To address this, Professor Jongmin Kim’s team developed the “START platform" technology based on aptamers. Aptamers are short strands of nucleic acids (DNA or RNA) that bind specifically and strongly to target molecules, making them ideal components for sensors that require high selectivity. When an aptamer binds to its target, it triggers a structural change in the aptamer sensor such as folding or unwinding. The team leveraged this mechanism to create a platform that mimics natural biological interactions, detects various molecules, and regulates gene expression as easily as assembling Lego blocks.

Building on this foundational technology, the team successfully developed sensors capable of detecting drugs and antibiotics like theophylline and tetracycline as well as specific proteins such as MS2 produced by bacteria. These sensors are designed with both the specificity to accurately recognize and respond to their targets and the orthogonality to function independently without interference even when multiple sensors are used together. This allows for seamless monitoring and regulation of various biological signals, including logic circuits integrated with complex genetic networks.

Compared to existing technologies, the team's platform offers significant engineering potential. This platform enables tunable control over both the sensitivity and the intensity of sensor response rather than simple detection of target biomolecules. Notably, the team was able to create novel biosensor components that follow simple design rules unlike natural counterparts in biological systems.

Professor Jongmin Kim of POSTECH stated "This study opens up new possibilities for the development of synthetic biosensors and the design of microbial genetic circuits." He added, "We will continue to explore applications in microbial engineering technologies including smart probiotics and metabolic engineering." 

The research was conducted with research grant from the Ministry of Science and ICT and the National Research Foundation of Korea and with support from the Korea Basic Science Institute’s project and LINC 3.0 of the Ministry of Education, the Korea Health Technology R&D Program of the Korea Health Industry Development Institute, the Program for Fostering and Supporting Food Tech R&D Centers of Gyeongsangbuk-do and Pohang, and the Institute for Basic Science of POSTECH.