title: Rule-based design of synthetic transcription factors in eukaryotes.
abstract: 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.
authors.affiliation: Department of Electrical Engineering & Computer Science and Department of Biological Engineering, Massachusetts Institute of Technology , 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States of America.
authors.forename: Oliver
authors.initials: O
authors.lastname: Purcell
authors.forename: Jean
authors.initials: J
authors.lastname: Peccoud
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Lu
mesh_terms: D017076:Computer-Aided Design; D015202:Protein Engineering; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics; D012984:Software; D058615:Synthetic Biology; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics
chemical_list: D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors
keywords: GenoCAD; Saccharomyces cerevisiae; eukaryotic transcription factor; grammar; synthetic transcription factor