Synthetic Biology: Foundations and Applications

Synthetic biology is an emerging engineering discipline for introducing novel functionalities into living systems. Synthetic biology promises to revolutionize our ability to leverage biology for a wide range of applications and our understanding of natural systems in disease and in health. Despite major progress over the last decade, significant challenges still hamper the design-build-test cycle for synthetic biology. These hurdles include poor predictive models, a lack of scalable parts libraries, inefficient circuit architectures, and low-throughput characterization techniques. To tackle these issues, we have focused our research on establishing scalable foundational platforms engineering biological systems. Extensible platforms for biological computation in living cells would enable new applications in biotechnology and new strategies for studying basic biology. We described scalable frameworks for eukaryotic transcriptional regulation and novel strategies for implementing digital and analog computation with synthetic gene circuits. We have developed synthetic transcriptional regulation platforms that enable scalable tuning of transcriptional activity, specificity, and cooperativity1. Our digital computational paradigm enables integrated cellular decision-making and logic in living cells and can be achieved with libraries of orthogonal recombinases2. Our strategy for implementing analog computation enables wide-dynamic-range biosensing and complex mathematical functions with a parsimonious set of devices3. We envision that future efforts in synthetic biology will integrate both digital and analog computation into hybrid state-machines to achieve application-specific goals. Leveraging platform technologies enabled by synthetic biology, we have been pursuing applications in the areas of biomaterials, biomedicine, and diagnostics. We recently used engineered biofilms to synthesize and pattern biomaterials across multiple length scales which can be interfaced with abiotic materials. We have established several strategies for combating antibiotic-resistance with synthetic phages4,5 and identifying novel combinatorial drug targets which resensitize multi-drug-resistant bacteria to antibiotics. Finally, we have translated our engineered phage technologies to establish pathogen detection platforms with breakthrough performance compared with existing strategies6.