Synthetic biology methodology and model refinement based on microelectronic modeling tools and languages.

In microelectronics, the design of new systems is based on a proven time-tested design flow. The goal of this paper is to determine to what extend this design flow can be adapted to biosystem design. The presented methodology is based on a top-down approach and consists of starting with a behavioral description of the system to progressively refine it to its final low-level system representation, composed of DNA parts. To preserve accuracy and simplicity, the design flow relies on refined models of biological mechanisms, which can be expressed by the hardware description languages and simulation tools traditionally used in microelectronics. A case study, the complete modeling of a priority encoder, is presented to demonstrate the effectiveness of the method.

[1]  Luciano Lavagno,et al.  EDA for IC Implementation, Circuit Design, and ProcessTechnology (Electronic Design Automation for Integrated Circuits Handbook) , 2006 .

[2]  Christophe Lallement,et al.  Design methodology and modeling of synthetic biosystems , 2010 .

[3]  Mandy L. Wilson,et al.  GenoCAD for iGEM: a grammatical approach to the design of standard-compliant constructs , 2010, Nucleic acids research.

[4]  Peter J. Ashenden,et al.  The System Designer's Guide to VHDL-AMS , 2002 .

[5]  Rajesh Krishnan,et al.  Circuit development using biological components: Principles, models and experimental feasibility , 2007 .

[6]  Herbert M. Sauro,et al.  In-Fusion BioBrick assembly and re-engineering , 2010, Nucleic acids research.

[7]  T. Sera.  Zinc-finger-based artificial transcription factors and their applications. , 2009, Advanced drug delivery reviews.

[8]  Ken Kundert,et al.  The designer's guide to Verilog-AMS , 2004 .

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

[10]  J. E. Franca.  Integrated circuit teaching through top-down design , 1994 .

[11]  Jacques Haiech,et al.  Synthetic biology and microelectronics: A similar design flow , 2009, 2009 Joint IEEE North-East Workshop on Circuits and Systems and TAISA Conference.

[12]  Ehud Shapiro,et al.  Processing DNA molecules as text , 2010, Systems and Synthetic Biology.

[13]  Luciano Lavagno,et al.  EDA for IC System Design, Verification, and Testing , 2006 .

[14]  D. Endy,et al.  Refinement and standardization of synthetic biological parts and devices , 2008, Nature Biotechnology.

[15]  M. Elowitz,et al.  Reconstruction of genetic circuits , 2005, Nature.

[16]  J. Keasling,et al.  Engineering a mevalonate pathway in Escherichia coli for production of terpenoids , 2003, Nature Biotechnology.

[17]  Peter J. Ashenden,et al.  The Designer's Guide to VHDL , 1995 .

[18]  Thomas F. Knight,et al.  Idempotent Vector Design for Standard Assembly of Biobricks , 2003 .

[19]  Lingchong You,et al.  Engineering novel synthetic biological systems , 2007 .

[20]  Gregory D. Peterson,et al.  Engineering in the biological substrate: information processing in genetic circuits , 2004, Proceedings of the IEEE.

[21]  Edward M. Rubin,et al.  Genomics of cellulosic biofuels , 2008, Nature.

[22]  Jacques Haiech,et al.  Multi-abstraction modeling in synthetic biology , 2010, 2010 3rd International Symposium on Applied Sciences in Biomedical and Communication Technologies (ISABEL 2010).

[23]  Martin Fussenegger,et al.  BioLogic gates enable logical transcription control in mammalian cells , 2004, Biotechnology and bioengineering.

[24]  Eckart Zitzler,et al.  Design of a biological half adder , 2007 .

[25]  Wolfgang Rosenstiel,et al.  SystemC: methodologies and applications , 2003 .

[26]  Andrew J. Millar,et al.  Development of a novel biosensor for the detection of arsenic in drinking water , 2007 .

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

[28]  François Pêcheux,et al.  VHDL-AMS and Verilog-AMS as alternative hardware description languages for efficient modeling of multidiscipline systems , 2005, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[29]  Jacques Haiech,et al.  Design Methodology for synthetic biosystems , 2010, Proceedings of the 17th International Conference Mixed Design of Integrated Circuits and Systems - MIXDES 2010.

[30]  Christopher A. Voigt,et al.  Environmentally controlled invasion of cancer cells by engineered bacteria. , 2006, Journal of molecular biology.

[31]  C. A. Hutchinson,et al.  Genome transplantation in bacteria: changing one species to another. , 2007, Nature Reviews Microbiology.