(6bk) Enabling Technologies for High-Throughput Synthetic Biology and Metabolic Engineering: From Engineering Genomes and Pathways to Genetic Circuits

Cells can be programmed to dynamically respond to their surroundings and selectively manufacture useful biomolecules using the tools of synthetic biology and metabolic engineering. However, engineering these intricate biological systems remains challenging due to time-consuming DNA construction, toxicity of biomolecules, and a lack of algorithms to guide genetic design. I have developed technologies to address these limitations that leverage next-generation sequencing, directed genome-wide mapping, and statistical design algorithms. In combination, these approaches allow for model-guided optimization of massively multipart genetic systems and complex phenotypes. Additionally, these novel methods enabled approximately 1,000-fold more genetic variants to be built over previous approaches and reduced the engineering cycle from a month or more to a week. I have applied these techniques to engineer bacteria to perform a variety of tasks including: manufacture biofuel to high titer with improved productivity, acquire the ability to fix atmospheric nitrogen towards more sustainable agriculture, and perform complex digital logic circuitry in response to multiple chemical inputs. These technologies pave the way for a new scale in synthetic biology and provide a platform to rapidly engineer functional biological systems for new pharmaceutical and industrial applications.