SyntheticBiologyEngPOV

Report
A COMPUTER ENGINEER’S VIEW OF
SYNTHETIC BIOLOGY
NAWWAF KHARMA, PHD
ELEC. & COMPUTER ENG.
CONCORDIA UNIVERSITY.
WWW.DRKHARMA.COM
SEQUENCE 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 designs
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WHAT 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)
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CLOCKS
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Elowitz et al. (2000)
Wong et al. (2006)
COMBINATORIAL LOGIC (4 INPUTS/1 OUTPUT)
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Rinaudo et al. (2007)
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Rinaudo et al. (2007)
COMBINATORIAL LOGIC: RIBOZYME-BASED
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Win et al. (2008)
RIBOSOFT:
WWW.DRKHARMA.COM/RIBOSOFT
Temp example http://www.drkharma.com/ribosoft/results/4gs7
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1-BIT MEMORY
FIRST TOGGLE
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Gardner et al. (2000)
1-BIT MEMORY
FULL TOGGLE
A toggle (or T) flip-flop with a single
input that is also clocked
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1-BIT MEMORY:
YIEST CELL
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Ajo-Franklin et al. (2007)
N-BIT MEMORY: STATE OF DNA
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Ham et al. (2008)
RELIABLE WELLCHARACTERIZED
MODULES?
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Canton et al. (2008)
FUTURE WORK
Artificial Evolution of life-like Assembly language
computer programs ..
• Metabolism energy is processing time; matter is
memory space
• Homeostasis changes to instructions or data do not
affect stability of function, except gracefully
• Adaptation self-modification in response to experience
to enhance life-signs & performance
• Replication self-replication of original or current self ..
with variation allow for selection and hence ..
• Evolution to occur in a population of such programs.
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REFERENCES
Kaern et al. (2003): Mads Kærn,William J Blake, and J J Collins. “The Engineering of Gene Regulatory Networks.” Annual
Review of Biomedical Engineering 5:179–206.
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, 363–372.
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. 63:1215–1220.
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 21:2271–2276.
Kaesling et al. (2006): http://keaslinglab.lbl.gov/wiki/index.php/Synthetic_Biology_-_Devices_-_Pulse_Generator
Rinaudo 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.
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REFERENCES CONTINUED
Ham 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 Kærn, 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: 8414–8419.
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. 1–2: 29–31.
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: 10435–10440.
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. 1–2: pp. 74–78.
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REFERENCES CONTINUED
Alexic 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. 1–2: 87–
90.
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:
10955–10960.
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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