Logic Gates - Emma Garren

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Logic Gates in Synthetic Biology

Background: Logic Gates and Truth Tables

A logic gate, the building block for digital circuits, is a computing unit that performs a logical operation on one or more inputs and produces a single output. Gates are identified by their function, and each type of logic gate can be represented with a distinctive symbol. The inputs are represented with short line segments to the left of the shape, and the output is represented by a short line segment to the right of the shape. A small circle on the right indicates that the output of the logical operation is inverted. Here are a few examples:



A truth table is a useful way to describe the behavior or function of a logic gate. A "1" is used for "true" or a positive input, and a "0" is used for "false" or a negative input.

Logic Gates in Synthetic Biology

Engineering Principles

  1. Standardization of parts
  2. Component abstraction
  3. Separation of system design from system fabrication


Biomolecular logic gates can be used as "parts" in the design of synthetic gene circuits.

Synthetic biology research is hindered by the inability to predict the functions of even simple devices and modules within the cellular environment, because of the influence of gene expression noise, mutation, cell death, undefined and changing extracellular environments, and interactions with the cellular context (Adrianantoandro et al., 2006).

Biomolecular Logic Gates: In Vitro

In vitro studies have been used to design combinations of molecules that have emergent properties related to information processing--molecular computing devices. The extent to which these devices will be used with the cellular context is unclear--however, they are bound to inspire new directions for research in synthetic biology.

Computing with Enzymes

Baron et al.

Ribozyme-Based Logic Gates

Stojanovic and Stephanovic

Synthetic Signaling Proteins

Dueber et al. - engineering synthetic signaling proteins with ultrasensitive input/output control.

DNA Self-Assembly

Yan et al. Seelig et. al.

DNA-Based Logic Gates

Frezza et al. Yoshida and Yokobayashi

Cellular Logic Gates

Oscillators and Bistable Switches

Elowitz and Leibler Collins - toggle switch

Artificial Cellular Communication Networks

Quorum-sensing as input for logical operation

Logic Gates in Mammalian Cells

Fusseneger

Applications and Future Directions

Synthetic gene circuits - use multiple simple input-output logic systems to design and build more complex circuits.

Medical applications - Increase specificity with which bacteria can sense an environment by combining multiple environmental inputs in logic gates. Autonomous biomolecular computing devices - use for molecular-level diagnostics and treatment

References

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  • Andrianantoandro, E., Subhayu, B., Karig, D. K., Weiss, R. (2006). Synthetic biology: new engineering rules for an emerging discipline. Mol Syst. Biol. 2:2006.0028. Abstract
  • Ashkenasy, G., Ghadiri, M. R. (2004). Boolean Logic Functions of a Synthetic Peptide Network. J Am Chem Soc. 126(36):11140-1. Abstract
  • Baron, R., Lioubashevski, O., Katz, E., Niazov, T., Willner, I. (2006). Two coupled enzymes perform in parallel the “AND” and “InhibAND” logic gate operations. Org Biomol Chem. 4(6): 989-91. Abstract
  • Baron, R., Lioubashevski, O., Katz, E., Niazov, T., Willner, I. (2006). Logic gates and elementary computing by enzymes. J Phys Chem A. 110(27):8548-53. Abstract
  • Boczko, E., Gedeon, T., Mischaikow, K. (2007). Dynamics of a simple regulatory switch. J Math Biol. 55(5-6):679-719. Abstract
  • Chen, X., Wang, Y., Liu, Q., Zhang, Z., Fan, C., He, L. (2006). Construction of molecular logic gates with a DNA-cleaving deoxyribozyme. Angew Chem Int Ed Engl. 45(11):1759-62. Abstract
  • Davidson, E.A., Ellington, A.D. (2007). Synthetic RNA circuits. Nat Chem Biol. 3(1):23-8. Abstract
  • Drubin, D. A., Way, J. C., Silver, P. A. (2007). Designing biological systems. Genes Dev. 21(3):242-54. Abstract
  • Elowitz, M. B., & Leibler, S. (2000). A synthetic oscillatory network of transcriptional regulators. Nature. 403(6767):335-8. Abstract
  • Farfel, J., Stefanovic, D. (2005). Towards practical biomolecular computers using microfluidic deoxyribozyme logic gate networks. University of New Mexico.
  • Frezza, B.M., Cockroft, S. L., Ghadiri, M.R. (2007). Modular Multi-level Circuits from Immobilized DNA-Based Logic Gates. J Am Chem Soc. (Epub ahead of print) Abstract
  • Gardner, T.S., Cantor, C.R., Collins, J.J. (2000). Construction of a genetic toggle switch in Escherichia coli. Nature. 403(6767):338-42. Abstract
  • Heinemann, M., Panke, S. (2006). Synthetic biology—putting engineering into biology. Bioinformatics. 22(22):2790-9. Abstract
  • Kaznessis, Y. N. (2007). Models for synthetic biology. BMC Syst Biol. 1(1):47. Abstract
  • Kramer, B. P., Fischer, C., Fussenegger, M. (2004). BioLogic Gates Enable Transcription Control in Mammalian Cells. Biotechnol Bioeng. 87(4):478-84. Abstract
  • Lederman, H., Macdonald, J., Stefanovic, D., Stojanovic, M. N. (2006). Deoxyribozyme-based three-input logic gates and construction of a molecular full adder. Biochemistry. 45(4):1194-9. Abstract
  • Narayanaswamy, R., Ellington, A.D. (2006). Engineering RNA-based circuits. Handb Exp Pharmacol. (173):423-45. Abstract
  • Rackham, O., Chin, J. W. (2005). Cellular logic with orthogonal ribosomes. JACS 1227:17584-85. Abstract
  • Sayut, D.J., Kambam, P.K., Sun, L. (2007). Engineering and applications of genetic circuits. Mol Biosyst. 3(12):835-840. Abstract
  • Seelig G., Soloveichik, D., Zhang, D. Y., Winfree, E., (2006). Enzyme-free nucleic acid logic circuits. Science. 314(5805): 1585-8. Abstract
  • Stojanovic, M. N., Semova, S., Kolpashchikov, D., Macdonald, J., Morgan, C., Stefanovic, D. (2005). Deoxyribozyme-based ligase logic gates and their initial circuits. J Am Chem Soc. 127(19):6914-5. Abstract
  • Voigt, C. A. (2006). Genetic parts to program bacteria. Curr Opin Biotechnol. 17:548-557. Abstract
  • Wall, M. E., Hlavacek, W. S., Savageau, M. A. (2004). Design of gene circuits: lessons from bacteria. Nat Rev Genet. 5(1):34-42. Abstract
  • Yoshida, W., Yokobayashi, Y. (2007). Photon Boolean logic gates based on DNA aptamers. Chem Commun (Camb). (2):195-7. Abstract
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