We engineer cell factories to produce several value-added proteins or chemicals. In our lab, we have engineered the cells to produce bacterial collagen which has been reported to be a promising substitute to mammalian collagen and has been tested as non-toxic, biocompatible and with a cell-specific adhesion capability with improved spreading effects. We have also engineered cells to produce different flavonoids including vanillin which is main chemical compound of vanilla extract and can be used as chemical intermediate in the manufacture of several important drugs and other products.

The design–build–test cycle of synthetic biology has enabled bio production of a diverse range of valuable products. However, due to the complex nature of the biological systems, it is always difficult to engineer a new biological system as predicted. Thus, testing and screening platforms have been placed on higher demands. Although the conventional testing and screening have been facilitated by automation solutions (such as liquid handler and colony picker), it is still tedious, costly, and time consuming. More importantly, the throughput has not met the requirement to make engineering new microbes economically viable. We have built an ultra-high throughput screening system, which has many advantages over existing screening methods, such as miniaturized reaction volume (total cell culture, reagent volume for 1,000,000 droplets screening is less than 5 mL), plastic consumables saving (a few of 1.5 mL tubes are sufficient for the screening process), and ultra-high throughput (1,000,000 droplets screening within 1 day) which is envisioned to have great applications in biomanufacturing.

Using light to control gene expression offers several advantages as compared to the traditional chemical-based control. Light system allows rapid transmission to cells, easy tuning of the intensity and pattern to generate reversible, temporal and spatial control of gene expression. We have optogenetics to control the production of recombinant bacterial collagen to improve protein folding and reduce cellular burden. Besides, we have developed blue light-mediated system to regulate the production of colanic acid to control the biofilm formation and thickness.

Biofilm reactors have shown to achieve higher productivity and longer production time than conventional bioreactors. However, uncontrolled growth of biofilms remains a key challenge in the application of biofilm in bioproduction. To address this problem, we developed light-controlled synthetic gene circuits to control biofilm formation and thickness by regulating the production of colanic acid, which is a key polysaccharide in E. coli biofilm extracellular polymeric substance (EPS). This approach has great potential as a new means to control and maintain biofilm thickness in biofilm related applications.

The rapid emergence of an increasing number of resistant bacteria is accelerating the arrival of the “post-antibiotic era”. New strategies to fight emerging pathogens are therefore of the utmost importance. Using a synthetic biology approach, we rationally design bacterial constructs to fight potentially deadly pathogens such as V. cholerae. Using harmless E. coli strains, our constructs sense the V. cholerae CAI-1 quorum sensing autoinducer and release the antibacterial protein Art-085 protein to kill the pathogen. This strategy allows to exert an antibacterial effect only when it is needed, therefore preventing development of resistance.

To actuate in an effective manner, our engineered cells need to sense their environment. By investigating and repurposing different sensor systems found in nature, we provide our engineered cells with the capability to sense our compound of interest. One example is our Vibrio cholerae biosensor. To sense this potentially deadly pathogen we adapt the CAI-1 quorum sensing mechanism of V. cholerae and incorporate it into our cell constructs, adapting it to our needs using a CRISPRi inverter. We have also engineered human commensal microbe that can specifically sense and kill an antibiotic-resistant strain of P. aeruginosa.

DNA data storage is an exciting new concept that aims to store our everyday information into the fabric of life itself – DNA. The immense density of DNA (215 petabytes per gram), its longevity (potentially millions of years in the appropriate conditions) as well as eternal biological relevance has led to significant interest in the area. We are developing synbio technology to exploit the use of DNA for data storage. The intent is to address the pressing issue with the impending shortage of silica necessary for manufacturing storage devices required to accommodate our projected data storage requirements. We in Poh lab are utilizing novel optogenetic tools, barcoding of bacterial cells, and spatial transcriptomics to provide an alternative approach to storing information into DNA – analogous to creating a camera for capturing and storing images directly into DNA itself.

Modeling in synthetic biology constitutes a powerful means in our continuous search for improved performance with a rational Design–Build–Test–Learn approach. However, a systematic yet modular pipeline that allows one to identify the appropriate model and guide the experimental designs while tracing the entire model development and analysis is still lacking. We have developed BMSS2, a unified tool that streamlines and automates model selection by combining information criterion ranking with upstream and parallel analysis algorithms. These include Bayesian parameter inference, a priori and a posteriori identifiability analysis, and global sensitivity analysis. The database-driven design supports interactive model storage/retrieval to encourage reusability and facilitate automated model selection.

Mathematical modelling allows a representative construct of the essential aspects of the system, capturing the system behaviour in a quantitative manner and allowing system analysis and rational design optimization. A well-implemented model is able to recapitulate essential system behaviours, and provide insights to specific questions about the system, as well as to generate new hypotheses. In our lab, mathematical modelling forms an integral part of most of the projects, e.g., biosensors and bioproduction in guiding the rational design of different constructs and providing insights of the system behaviours. Modelling tools have also been developed to facilitate the model development and analysis.