Abstract
We propose a mapping from digital logic circuits into genetic regulatory networks with the following property: the chemical activity of such a genetic network in vivo implements the computation specified by the corresponding digital circuit. Logic signals are represented by the synthesis rates of cytoplasmic DNA binding proteins. Gates consist of structural genes for output proteins, fused to promoter/operator regions that are regulated by input proteins. The modular approach for building gates allows a free choice of signal proteins and thus enables the construction of complex circuits. This paper presents simulation results that demonstrate the feasibility of this approach. Furthermore, a technique for measuring gate input/output characteristics is introduced. We will use this technique to evaluate gates constructed in our laboratory. Finally, this paper outlines automated logic design and presents BioSpice, a prototype system for the design and verification of genetic digital circuits.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
A. Arkin and J. Ross. Computational functions in biochemical reaction net-works. Biophysical Journal, 67:560–578, August 1994.
James U. Bowie and Robert T. Sauer. Identification of C-terminal extensionsthat protect proteins from intracellular proteolysis. Journal of Biological Chemistry, 264(13):7596–7602, 1989.
David E. Draper. Translational initiation. In Frederick C. Neidhardt, editor, Escherichia Coli and Salmonella, pages 902–908. ASM Press, Washington, D.C., 2nd edition, 1992.
Alice Longobardi Givan. Flow Cytometry: First Principles. Wiley-Liss, New York, 1992.
Roger W. Hendrix. Lambda IL Cold Spring Harbor Press, Cold Spring Harbor, New York, 1983.
Peter H. von Hippel, Thomas D. Yager, and Stanley C. Gill. Quantitative aspects of the transcription cycle in Escherichia coli. In Transcriptional Regulation, pages 179–201. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1992.
A. Hjelmfelt, E. D. Weinberger, and J. Ross. Chemical implementation of neural networks and Turing machines. Proc. Natl. Acad. Sei., 88:10983–10987, December 1991.
M. Thomas Record Jr., Wilham S. Reznikoff, Maria L. Craig, Kristi L. McQuade, and Paula J. Schlax. Escherichia coli RNA polymerase (eσ 70), promoters, and the kinetics of the steps of transcription initiation. In Frederick C. Neidhardt, editor, Escherichia coli and Salmonella, pages 792–821. ASM Press, Washington, D.C., 2nd edition, 1992.
S. A. Kauffman. Gene regulation networks: a theory for their global structure and bahviors. In A. Moscona and A. Monroy, editors. Current Topics in Developmental Biology, volume 6, pages 145–182. Academic Press, New York, 1971.
Thomas F. Knight, Jr. and Gerald Jay Sussman. Cellular gate technology. In C.S. Calude, J. Casti, and M.J. Dinneen, editors. First International Conference on Unconventional Models of Computation, pages 257–272, Auckland, NZ, 1998. Springer-Verlag.
Harley H. McAdams and Adam Arkin. Stochastic mechanisms in gene expression. Proc. Natl. Acad. Sei., 94:814–819, February 1997.
Harley H. McAdams and Adam Arkin. Simulation of prokaryotic genetic circuits. Annu. Rev. Biophys. Biomol. Struc, 27:199–224, 1998.
Harley H. McAdams and Lucy Shapiro. Circuit simulation of genetic networks. Science, 269(5224):650–656, August 1995.
J. Monod and F. Jacob. Cellular Regulatory Mechanisms, pages 389–401. Cold Spring Harbor Press, New York, 1961.
Frederick C. Neidhardt and Michael A. Savageau. Regulation beyond the Operon. In Frederick C. Neidhardt, editor, Escherichia coli and Salmonella, pages 1310–1324. ASM Press, Washington, D.C., 2nd edition, 1992.
Andrew A. Pakula and Robert T. Sauer. Genetic analysis of protein stability and function. Annual Review of Genetics, 23:289–310, 1989.
Dawn A. Parsell, Karen R. Silber, and Robert T. Sauer. Carboxy-terminal determinants of intracellular protein degradation. Genes and Development, 4:277–286, 1990.
Mark Ptashne. A Genetic Switch: Phage lambda and Higher Organisms. Cell Press and Blackwell Scientific Publications, Cambridge, MA, 2nd edition, 1986.
O. Roessler. J. Theor. Biol., 36:413–417, 1972.
O. Roessler. In M. Conrad, W. Guettinger, and M. Dal Cin, editors. Lecture Notes in Biomathematics 4, pages 399–418. Springer, Berlin, 1974.
O. Roessler. In M. Conrad, W. Guettinger, and M. Dal Cin, editors. Lecture Notes in Biomathematics 4, pages 546–582. Springer, Berlin, 1974.
F. Seelig and O. Roessler. Z. Naturforsch, 27:1441–1444, 1972.
M. Sugita. Functional analysis of chemical systems in vivo using a logic circuit equivalent. J. Theor. Biol., 4:179–192, 1963.
R. Thomas. Boolean formalization of genetic control circuits. J. Theor. Biol, 42:563–585, 1973.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Weiss, R., Homsy, G.E., Knight, T.F. (2002). Toward in vivo Digital Circuits. In: Landweber, L.F., Winfree, E. (eds) Evolution as Computation. Natural Computing Series. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55606-7_14
Download citation
DOI: https://doi.org/10.1007/978-3-642-55606-7_14
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-63081-1
Online ISBN: 978-3-642-55606-7
eBook Packages: Springer Book Archive