Synthetic biology: A Computer Engineers Perspective

A Computer Engineers view of synthetic biology

Nawwaf kharma, PhDElec. & Computer Eng.Concordia university.www.drkharma.com1Sequence Detector (111)Design and build a cell that would detect the sequence 111(A) Follow a traditional (now fully automated) computer engineering design process(B) Identify the biological components (essentially gene networks) needed to realize such designs2

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1010What is needed(1) Synchronizing clock(2) Logic gates (e.g., {AND, OR, NOT})(3) Read/Write Memory (e.g., D flip-flop)(4) Communications (signals)(5) Input / Output (Sense / Report)11CLOCKS

Elowitz et al. (2000) Wong et al. (2006)

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Combinatorial Logic (4 inputs/1 output)

Rinaudo et al. (2007)1313

Rinaudo et al. (2007)1414Combinatorial logic: Ribozyme-based

Win et al. (2008)

1515RiboSoft:

www.drkharma.com/ribosoft16Temp example http://www.drkharma.com/ribosoft/results/4gs71-bit memoryFirst Toggle

Gardner et al. (2000)

17171-bit memoryFull toggleA toggle (or T) flip-flop with a single input that is also clocked18

1-bit memory:Yiest cell

Ajo-Franklin et al. (2007)1919N-bit memory: state of DNA

Ham et al. (2008)2020Reliable Well-Characterized Modules?

Canton et al. (2008)2121Future workArtificial Evolution of life-like Assembly language computer programs ..Metabolism energy is processing time; matter is memory spaceHomeostasis changes to instructions or data do not affect stability of function, except gracefullyAdaptation self-modification in response to experience to enhance life-signs & performanceReplication self-replication of original or current self .. with variation allow for selection and hence ..Evolution to occur in a population of such programs.

22ReferencesKaern et al. (2003): Mads Krn,William J Blake, and J J Collins. The Engineering of Gene Regulatory Networks. Annual Review of Biomedical Engineering 5:179206.Deans et al. (2007): Tara L Deans, Charles R Cantor & James J Collins. A Tunable Genetic Switch Based on RNAi and Repressor Proteins for Regulating Gene Expression in Mammalian Cells. Cell 130, 363372.Win et al. (2008): Maung Nyan Win & Christina D Smolke. Higher-Order Cellular Information Processing with Synthetic RNA Devices. Science vol. 322, 456-460.Gardner et al. (2000): Timothy S Gardner, Charles R Cantor & James J Collin. Construction of a genetic toggle switch in Escherichia coli. Nature vol. 403, 339-342.Elowitz et al. (2000): Michael B Elowitz & Stanislas Leibler. A synthetic oscillatory network of transcriptional regulators. Nature vol. 403, 335- 338.Wong et al. (2006): W W Wong and J C Liao. The design of intracellular oscillators that interact with metabolism. Cell. Mol. Life Sci. vol. 63:12151220.Ajo-Franklin et al. (2007): Caroline M Ajo-Franklin, David A Drubin, Julian A Eskin, Elaine P S Gee, Dirk Landgraf, Ira Phillips & Pamela A Silver. Rational design of memory in eukaryotic cells. Genes and Development 21:22712276.Kaesling et al. (2006): http://keaslinglab.lbl.gov/wiki/index.php/Synthetic_Biology_-_Devices_-_Pulse_GeneratorRinaudo et al. (2007): Keller Rinaudo, Leonidas Bleris, Rohan Maddamsetti, Sairam Subramanian, Ron Weiss & Yaakov Benenson. A universal RNAi-based logic evaluator that operates in mammalian cells. Nature Biotechnology vol. 25, No. 7: 795-801.

2323References continuedHam et al. (2008): Timothy S Ham, Sung K Lee, Jay D Keasling & Adam P Arkin. Design and Construction of a Double Inversion Recombination Switch for Heritable Sequential Genetic Memory. PloS ONE, vol. 3, No. 7: 1-9.Kobayashi et al. (2004): Hideki Kobayashi, Mads Krn, Michihiro Araki, Kristy Chung, Timothy S Gardner, Charles R Cantor & James J Collins. Programmable cells: Interfacing natural and engineered gene networks. PNAS vol. 101, No. 22: 84148419.Basu et al. (2005): Subhayu Basu, Yoram Gerchman, Cynthia H Collins, Frances H Arnold & Ron Weiss. A synthetic multicellular system for programmed pattern formation. Nature, vol. 434: 1130-1134. IET Synth. Biol., vol. 1, no. 12: 2931.Bernhardt et al. (2007): K Bernhardt, E J Carter, N S Chand, J Lee, Y Xu, X Zhu, J W Ajioka, J M Goncalves, J Haseloff, G Micklem and D Rowe. New tools for self-organised pattern formation. Weber et al. (2007): Wilfried Weber, Marie Daoud-El Baba & Martin Fussenegger. Synthetic ecosystems based on airborne inter- and intrakingdom communication. PNAS, vol. 104, no. 25: 1043510440. Rodrigo et al. (2007): G Rodrigo, A Montagud, A Aparici, M C Aroca, M Baguena, J Carrera, C Edo, P Fernandez-de-Cordoba, A Ferrando, G Fuertes, D Gimenez, C Mata, J V Medrano, C Navarrete, E Navarro, J Salgado, P Tortosa, J Urchueguia and A Jaramillo. Vanillin cell sensor. IET Synth. Biol., vol. 1, no. 12: pp. 7478.

2424References continuedAlexic et al. (2007): J Aleksic, F Bizzari, Y Cai, B Davidson, K de Mora, S. Ivakhno, S L Seshasayee, J Nicholson, J Wilson, A Elfick, C French, L Kozma-Bognar, H Ma & A Millar. Development of a novel biosensor for the detection of arsenic in drinking water. IET Synthetic Biolology, vol. 1, no. 12: 8790.Canton et al. (2008): Barry Canton, Anna Labno & Drew Endy. Refinement and standardization of synthetic biological parts and devices. Nature Biotechnology, vol. 26, no. 7: 787-793.Garcia-Ojalvo et al. (2004): Jordi Garcia-Ojalvo, Michael B Elowitz, and Steven H Strogatz. Modeling a synthetic multicellular clock: Repressilators coupled by quorum sensing. PNAS, vol. 101, no. 30: 1095510960.Weber et al. (2009): Wilfried Weber, Stefan Luzi, Maria Karlsson, Carlota Diaz Sanchez-Bustamante, Urs Frey, Andreas Hierlemann & Martin Fussenegger. A synthetic mammalian electro-genetic transcription circuit. Nucleic Acids Research, vol. 37, no. 4.

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