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of biological circuits that perform specified functions reliably is not well developed. As one example, there is not a comprehensive knowledge-base that guides the selection between transcriptional, post-transcriptional, or posttranslational control schemes or layering of these schemes to achieve a desired circuit performance.

The engineering of microbial chemical factories provides important case examples of engineering complex biological systems. Researchers are successfully engineering complex metabolic pathways (comprising up to 10-20 synthetic enzymatic steps) in microorganisms to achieve bioremediation and green synthesis strategies, the latter directed to the synthesis of various specialty drugs and chemical commodities, including biofuels. One recent example is based on the engineering of microorganisms, such as yeast and bacteria, to produce a cure for malaria based on the natural product artemisinin. Artemisinin is a molecule that is naturally produced in the plant Artemisia annua and is obtained through extraction from the plant material. Currently, the drug is expensive and thus does not allow effective treatment of malaria in the third world countries most afflicted with this disease. Researchers developed a solution to this problem by engineering a microorganism that can be grown cheaply, quickly, and in very large volumes to produce Artemisinin at nearly one-tenth of its current price. However, the success of this single engineering effort (and the current design, construction, and optimization processes in place) required a very large amount of dedicated resources and time. Therefore, the investment required to apply this strategy anew to every chemical and material we would like to produce is unrealistic with current technologies. As such, the ability of newly developed foundational technologies that will make these approaches cheaper, faster, and more reliable is critical to the broader application of synthetic biology.

Key Questions

  • What are the most important experimental and computational technologies and tools that will support the engineering of biological systems?

  • What new technologies are required to support increased efficiencies and scaling in design, construction, and optimization of biological processes?

  • What tools are most needed to address the growing gap between our ability to construct and our ability to design large-scale integrated biological systems?

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