Researchers have created a new technology that enhances the accuracy and integration density of synthetic genetic circuits.
Professor Jongmin Kim’s research team at POSTECH has developed a novel technology to enhance the accuracy and integration density of synthetic genetic circuits.
The team, led by Professor Jongmin Kim from the Department of Life Sciences at POSTECH, along with graduate students Hyunseop Goh and Seungdo Choi, has introduced the ‘Synthetic Translational Coupling Element (SynTCE).’ This innovation significantly improves the accuracy and integration density of genetic circuits used in synthetic biology. Their findings have recently been published in ‘Nucleic Acids Research’, an esteemed journal in the fields of molecular biology and biochemistry.
‘Synthetic biology’ is a discipline that assigns new capabilities to organisms by utilizing both natural and engineered genetic regulatory tools. Organisms modified through synthetic biology have applications in a variety of areas, such as treating diseases, creating microorganisms that can degrade plastic, and producing biofuels. One key aspect is the ‘polycistronic operon’ system, wherein multiple genes are expressed together to form complexes that execute specific functions, thereby optimizing encoding efficiency with minimal resources.
Nevertheless, designing complex genetic circuits requires minimizing interference among biological components and enhancing encoding density for effective integration of gene circuits. The use of synthetic RNA-based translation regulatory components often faces challenges in managing multiple genes and achieving high precision due to disruptions in the protein translation process.
In response to this challenge, Professor Kim’s team investigated ‘translational coupling,’ a natural regulatory mechanism found in operons managing multiple genes, where the translation of genes ahead affects the translation efficiency of subsequent genes. Through this study, the team created the ‘SynTCE’ that emulates this mechanism and successfully incorporated it with synthetic biological RNA devices to construct more effective genetic circuits.
By embedding SynTCE structure in an RNA computing framework that the team had previously detailed, the integration density of genetic circuits is significantly improved. SynTCE facilitates precise signal transmission to downstream genes, allowing for unprecedented control over multiple inputs and outputs within a single RNA molecule.
Interestingly, by accurately managing protein N-terminals and reducing translation interference, SynTCE could be utilized in ‘biological containment’ technologies. This application can selectively target and eliminate specific cells, as well as direct proteins to predetermined cellular locations. This technology is anticipated to enhance precise functional control and support desired biological manipulations within cells.
Professor Jongmin Kim remarked, “This research signifies a major advancement in the design of complex and precise genetic circuits.” He also expressed optimism that “this new design will find applications in diverse fields such as custom cell therapeutics, bioremediation microorganisms, and the production of biofuels.”
This research received backing from various organizations, which include the Institute of Planning and Evaluation for Technology in Food, Agriculture, and Forestry, the National Research Foundation of Korea, synthetic biology funding from Gyeongsangbuk-do and Pohang City, the Korea Health Industry Development Institute’s Health Technology R&D Project, support from Gyeongbuk Techno Park, the Ministry of Education’s 4th BK21 project, the Korea Basic Science Institute project, and the Leaders In Industry-University Cooperation 3.0 (LINC 3.0).
