Towards programming languages for genetic engineering of living cells

Synthetic biology aims at producing novel biological systems to carry out some desired and well-defined functions. An ultimate dream is to design these systems at a high level of abstraction using engineering-based tools and programming languages, press a button, and have the design translated to DNA sequences that can be synthesized and put to work in living cells. We introduce such a programming language, which allows logical interactions between potentially undetermined proteins and genes to be expressed in a modular manner. Programs can be translated by a compiler into sequences of standard biological parts, a process that relies on logic programming and prototype databases that contain known biological parts and protein interactions. Programs can also be translated to reactions, allowing simulations to be carried out. While current limitations on available data prevent full use of the language in practical applications, the language can be used to develop formal models of synthetic systems, which are otherwise often presented by informal notations. The language can also serve as a concrete proposal on which future language designs can be discussed, and can help to guide the emerging standard of biological parts which so far has focused on biological, rather than logical, properties of parts.

[1]  D Garfinkel,et al.  A machine-independent language for the simulation of complex chemical and biochemical systems. , 1968, Computers and biomedical research, an international journal.

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

[3]  Herbert M. Sauro,et al.  33 JARNAC: a system for interactive metabolic analysis , 2000 .

[4]  Aviv Regev,et al.  Representation and Simulation of Biochemical Processes Using the pi-Calculus Process Algebra , 2000, Pacific Symposium on Biocomputing.

[5]  H. Afif,et al.  The ratio between CcdA and CcdB modulates the transcriptional repression of the ccd poison–antidote system , 2001, Molecular microbiology.

[6]  Nicolas E. Buchler,et al.  On schemes of combinatorial transcription logic , 2003, Proceedings of the National Academy of Sciences of the United States of America.

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

[8]  François Fages,et al.  The Biochemical Abstract Machine BIOCHAM , 2004, CMSB.

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

[10]  Pieter Rein ten Wolde,et al.  Transcriptional Regulation by Competing Transcription Factor Modules , 2006, PLoS Comput. Biol..

[11]  Krzysztof R. Apt,et al.  Constraint logic programming using Eclipse , 2007 .

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

[13]  L. F. Perrone,et al.  SBW – A MODULAR FRAMEWORK FOR SYSTEMS BIOLOGY , 2006 .

[14]  M. Elowitz,et al.  Programming gene expression with combinatorial promoters , 2007, Molecular systems biology.

[15]  R. Waldinger,et al.  Deductive Biocomputing , 2007, PloS one.

[16]  Frederick K. Balagaddé,et al.  Biology by design: reduction and synthesis of cellular components and behaviour , 2007, Journal of The Royal Society Interface.

[17]  T. Henzinger,et al.  Executable cell biology , 2007, Nature Biotechnology.

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

[19]  Vincent Danos,et al.  Rule-Based Modelling of Cellular Signalling , 2007, CONCUR.

[20]  Michael Hucka,et al.  LibSBML: an API Library for SBML , 2008, Bioinform..

[21]  Gordon D. Plotkin,et al.  A Language for Biochemical Systems , 2008, CMSB.

[22]  Jeremy Gunawardena,et al.  Programming with models: modularity and abstraction provide powerful capabilities for systems biology , 2009, Journal of The Royal Society Interface.

[23]  Mat E. Barnet,et al.  A synthetic Escherichia coli predator–prey ecosystem , 2008, Molecular systems biology.

[24]  Jörg Stelling,et al.  Computational design of synthetic gene circuits with composable parts , 2008, Bioinform..

[25]  Jane Hillston,et al.  Bio-PEPA: An Extension of the Process Algebra PEPA for Biochemical Networks , 2007, FBTC@CONCUR.

[26]  Luca Cardelli,et al.  Compositionality, stochasticity, and cooperativity in dynamic models of gene regulation , 2007, HFSP journal.