(72a) Engineering Biological Systems: The Increasing Role of Design in a Time of Paradigm Shifting Technology

Technologies for synthesizing and sequencing DNA have advanced faster than Moore's law, resulting in completely new ways of thinking about how to go about engineering microbial genomes. For example, the first complete microbial genome was synthesized and successfully transplanted into a host chassis in 2010 at a cost of ~$10-100 million. In just 3 years, synthesis technology has advanced to the point that it is now expected that sufficient DNA to construct full genomes will be available at costs 100,000x lower and in turn-around times of weeks.  Sequencing has advanced even further, with the latest technologies proposing full-genome microbial sequencing for under $100. Along with improved methods for screening, sorting, and characterizing cells, the throughput of the biological design-build-test cycle has increased by several orders of magnitude. Such capabilities require a shift in thinking at the most basic level about how to pursue microbial systems engineering, with much recent inspiration in this arena drawn from computer science and engineering, and specifically throughout the rapidly expanding field of synthetic biology. While synthetic biology approaches have focused primarily on a ground-up approach to cellular engineering, metabolic engineering and systems biology have emphasized engineering strategies that emphasize the performance of the overall system as a starting point. Future efforts will bridge these two paradigms, with the initial step focusing on rigorous design efforts that not only attempt to connect well characterized biological parts to overall performance through systems modeling but also on design search algorithms that guide design-build-test-learn cycles in a manner that increases understanding and furthers the engineering effort. Our efforts are focused on developing technologies and approaches that enable this vision. This presentation will describe several of our efforts in this area, as well as provide recent data on application areas we are pursuing including the biological production of chemicals and fuels.