Barcoding Strategy Speeds, Reduces Cost for Testing New Designs in Synthetic Biology

Achievement date: 

Researchers at the University of California (UC) Berkeley have developed microscope-readable barcodes, or MiCodes, in engineered cells that enable much more rapid testing of novel synthetic biology designs than ever before, speeding the pace of advances in a wide variety of bio-products, from industrial chemicals to pharmaceuticals.  This work was supported by the NSF-funded Synthetic Biology Engineering Research Center (Synberc), which is headquartered UC Berkeley.


Synthetic biology involves the application of engineering principles to biology, using many of the same tools and experimental techniques to build artificial biological systems. The focus is often on taking parts of natural biological systems, characterizing and simplifying them, and using them as components of an engineered biological system. While dramatic progress has been made in the design and build phases of the design–build–test cycle for engineering cells, limitations in the test phase were a significant barrier because many cells are not amenable to rapid analytical measurements. The new strategy enables researchers to “light up” discernible structures within living cells with MiCodes composed of fluorescent proteins, making analysis by microscopy possible.


The inherent complexity of biological systems and our limited understanding of the process of building complex, lower-level details from a high-level model or concept (i.e., “forward engineering”) usually require testing many designs to find one that yields the desired characteristics or traits (phenotypes) in an organism. Engineering cellular behaviors often demands the ability to measure a phenotype in individual cells. Methods such as fluorescence-activated cell sorting (FACS) have become powerful single-cell analytical tools that can automate screening and achieve high-throughput results. A limitation of these methods has been the requirement that the outputs of interest be fluorescent or able to be linked to fluorescent output. Many desirable cellular phenotypes were clearly visualized by microscopy, but lacked the fluorescent characteristic. By addressing the fluorescence issue, the new barcoding strategy makes parallel analysis of phenotypes of interest via microscopy possible.

As a first demonstration of the system, the researchers MiCoded a set of synthetic proteins to allow testing of a selection for specific interactions in mixed populations of cells. A novel microscopy-readable two-hybrid fluorescence localization assay for probing candidate interactions in the cell cytoplasm was also developed using a protein tagged with a fluorescent protein. This work introduces a generalizable, scalable platform for making microscopy amenable to higher-throughput screening experiments.