Genetic design: rising above the sequence.

Genetic engineering has developed around technologies enabling the targeted in vitro recombination of DNA molecules found in living organisms. As a result, the development of new DNA molecules has been primarily focused on cloning strategies that allow their assembly from existing DNA fragments. As chemical gene synthesis matures, the design of synthetic DNA molecules becomes the bottleneck of many biotechnology projects. It becomes urgent to develop representations of synthetic genetic systems more abstract than their DNA sequence. Abstraction makes it possible to reuse simple components to build complex systems or to break down a complex engineering problem into manageable tasks. Specialized computer languages or a general purpose XCell Description Language are promising avenues to build abstraction hierarchies for synthetic biology.

[1]  Matthias Heinemann,et al.  Synthetic biology - putting engineering into biology , 2006, Bioinform..

[2]  E. O’Shea,et al.  Living with noisy genes: how cells function reliably with inherent variability in gene expression. , 2007, Annual review of biophysics and biomolecular structure.

[3]  William H. Sanders,et al.  Dynamic partitioning for hybrid simulation of the bistable HIV-1 transactivation network , 2006, Bioinform..

[4]  David B. Searls,et al.  Grammatical Representations of Macromolecular Structure , 2006, J. Comput. Biol..

[5]  Kenneth Slonneger,et al.  Formal syntax and semantics of programming languages - a laboratory based approach , 1995 .

[6]  J. Beckmann,et al.  Linguistics of nucleotide sequences: morphology and comparison of vocabularies. , 1986, Journal of biomolecular structure & dynamics.

[7]  Bjarne Knudsen,et al.  RNA secondary structure prediction using stochastic context-free grammars and evolutionary history , 1999, Bioinform..

[8]  J. Collins,et al.  Construction of a genetic toggle switch in Escherichia coli , 2000, Nature.

[9]  J. Raser,et al.  Noise in Gene Expression: Origins, Consequences, and Control , 2005, Science.

[10]  Bjarne Knudsen,et al.  Pfold: RNA Secondary Structure Prediction Using Stochastic Context-Free Grammars , 2003 .

[11]  Alan Villalobos,et al.  Gene Designer: a synthetic biology tool for constructing artificial DNA segments , 2006, BMC Bioinformatics.

[12]  Patricia Adams,et al.  Programming Languages: Principles and Practice , 1993 .

[13]  M. Elowitz,et al.  A synthetic oscillatory network of transcriptional regulators , 2000, Nature.

[14]  David B. Searls,et al.  Linguistic approaches to biological sequences , 1997, Comput. Appl. Biosci..

[15]  George M Church,et al.  Synthetic biology projects in vitro. , 2006, Genome research.

[16]  David B. Searls,et al.  The Linguistics of DNA , 1992 .

[17]  Ron Weiss,et al.  Engineering life: building a fab for biology. , 2006, Scientific American.

[18]  Koji Kawabata,et al.  Complete Chemical Synthesis , Assembly , and Cloning of a Mycoplasma genitalium Genome , 2008 .

[19]  Sarah J Kodumal,et al.  Total synthesis of long DNA sequences: synthesis of a contiguous 32-kb polyketide synthase gene cluster. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[20]  D. Endy,et al.  Refactoring bacteriophage T7 , 2005, Molecular systems biology.

[21]  Mudita Singhal,et al.  COPASI - a COmplex PAthway SImulator , 2006, Bioinform..

[22]  Mark E. Cooper,et al.  Gene-to-phenotype models and complex trait genetics , 2005 .

[23]  J. Collado-Vides,et al.  Grammatical model of the regulation of gene expression. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[24]  D. Endy Foundations for engineering biology , 2005, Nature.

[25]  D. Searls,et al.  Robots in invertebrate neuroscience , 2002, Nature.

[26]  Kent Vander Velden,et al.  The selective values of alleles in a molecular network model are context dependent. , 2004, Genetics.

[27]  Hiroaki Kitano,et al.  The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models , 2003, Bioinform..

[28]  H. McAdams,et al.  Circuit simulation of genetic networks. , 1995, Science.

[29]  Peter Linz,et al.  An Introduction to Formal Languages and Automata , 1997 .

[30]  G. Seelig,et al.  Enzyme-Free Nucleic Acid Logic Circuits , 2022 .

[31]  Jean Peccoud,et al.  A syntactic model to design and verify synthetic genetic constructs derived from standard biological parts , 2007, Bioinform..

[32]  J. Boeke,et al.  GeneDesign: rapid, automated design of multikilobase synthetic genes. , 2006, Genome research.

[33]  J. Peccoud,et al.  Targeted Development of Registries of Biological Parts , 2008, PloS one.

[34]  D. Searls,et al.  Gene structure prediction by linguistic methods. , 1994, Genomics.

[35]  S. Govindarajan,et al.  Codon bias and heterologous protein expression. , 2004, Trends in biotechnology.

[36]  Alberto L. Sangiovanni-Vincentelli,et al.  The Tides of EDA , 2003, IEEE Des. Test Comput..

[37]  E. Andrianantoandro,et al.  Synthetic biology: new engineering rules for an emerging discipline , 2006, Molecular systems biology.

[38]  M. Elowitz,et al.  Combinatorial Synthesis of Genetic Networks , 2002, Science.

[39]  E. Tatum A case history in biological research. , 1958, Science.

[40]  V. Brendel,et al.  Genome structure described by formal languages. , 1984, Nucleic acids research.

[41]  Mario Gimona,et al.  Protein linguistics — a grammar for modular protein assembly? , 2006, Nature Reviews Molecular Cell Biology.

[42]  A. Arkin,et al.  Fast, cheap and somewhat in control , 2006, Genome Biology.