Rule-Based Design of Synthetic Transcription Factors in Eukaryotes

• Main Authors: Purcell, Oliver (Contributor), Peccoud, Jean (Author), Lu, Timothy K. (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science (Contributor), Massachusetts Institute of Technology. Research Laboratory of Electronics (Contributor), Massachusetts Institute of Technology. Synthetic Biology Center (Contributor)
• Format: Article
• Language: English
• Published: American Chemical Society (ACS), 2016-01-14T17:40:53Z.
• Subjects: Article
• Online Access: Get fulltext

To design and build living systems, synthetic biologists have at their disposal an increasingly large library of naturally derived and synthetic parts. These parts must be combined together in particular orders, orientations, and spacings to achieve desired functionalities. These structural constraints can be viewed as grammatical rules describing how to assemble parts together into larger functional units. Here, we develop a grammar for the design of synthetic transcription factors (sTFs) in eukaryotic cells and implement it within GenoCAD, a Computer-Aided Design (CAD) software for synthetic biology. Knowledge derived from experimental evidence was captured in this grammar to guide the user to create designer transcription factors that should operate as intended. The grammar can be easily updated and refined as our experience with using sTFs in different contexts increases. In combination with grammars that define other synthetic systems, we anticipate that this work will enable the more reliable, efficient, and automated design of synthetic cells with rich functionalities.
United States. Defense Advanced Research Projects Agency
National Institutes of Health (U.S.) (New Innovator Award 1DP2OD008435)
National Science Foundation (U.S.) (1124247)
United States. Office of Naval Research (N00014-13-1-0424)