GenoCAD: linguistic approaches to synthetic biology

Abstract

Synthetic biology is an emerging interdisciplinary research field, which leverages the maturation of DNA synthesis technologies. By introducing engineering principles to synthetic biological systems design, synthetic biology shows great potential to shed new lights on biology and benefit human beings. Computer assisted design (CAD) tools will play an important role in the rational design of synthetic genetic systems. This dissertation presents the first CAD tool for synthetic biology — GenoCAD, a linguistic-based web application. By viewing DNA sequences as a language, we developed the first syntactic model to design and verify synthetic genetic constructs. Then we conducted a careful curation of the terminal set in the grammar - the first comprehensive analysis of the Registry of standard biological parts. The implementation and major features of GenoCAD are discussed, and in particular we showed how to develop a domain-specific grammar for BioBrick-based construct design and make GenoCAD a useful tool for the iGEM students. Finally, we went beyond the syntactic level to explore the semantics of synthetic DNA sequences: by associating attributes with biological parts and coupling semantic actions with grammar rules, we developed the first semantic models to relate the genotype to the phenotype of synthetic genetic constructs. The theories and techniques presented in this dissertation, along with the informative results presented, will serve as a foundation for the future developments of GenoCAD.