Engineering bacteria to solve the Burnt Pancake Problem

Karmella Haynes, Marian L. Broderick, Adam D. Brown, Trevor L. Butner, James O. Dickson, W. Lance Harden, Lane H. Heard, Eric L. Jessen, Kelly J. Malloy, Brad J. Ogden, Sabriya Rosemond, Samantha Simpson, Erin Zwack, A. Malcolm Campbell, Todd T. Eckdahl, Laurie J. Heyer, Jeffrey L. Poet

Research output: Chapter in Book/Report/Conference proceedingChapter

35 Citations (Scopus)

Abstract

Background: We investigated the possibility of executing DNA-based computation in living cells by engineering Escherichia coli to address a classic mathematical puzzle called the Burnt Pancake Problem (BPP). The BPP is solved by sorting a stack of distinct objects (pancakes) into proper order and orientation using the minimum number of manipulations. Each manipulation reverses the order and orientation of one or more adjacent objects in the stack. We have designed a system that uses site-specific DNA recombination to mediate inversions of genetic elements that represent pancakes within plasmid DNA. Results: Inversions (or "flips") of the DNA fragment pancakes are driven by the Salmonella typhimurium Hin/hix DNA recombinase system that we reconstituted as a collection of modular genetic elements for use in E. coli. Our system sorts DNA segments by inversions to produce different permutations of a promoter and a tetracycline resistance coding region; E. coli cells become antibiotic resistant when the segments are properly sorted. Hin recombinase can mediate all possible inversion operations on adjacent flippable DNA fragments. Mathematical modeling predicts that the system reaches equilibrium after very few flips, where equal numbers of permutations are randomly sorted and unsorted. Semiquantitative PCR analysis of in vivo flipping suggests that inversion products accumulate on a time scale of hours or days rather than minutes. Conclusion: The Hin/hix system is a proof-of-concept demonstration of in vivo computation with the potential to be scaled up to accommodate larger and more challenging problems. Hin/hix may provide a flexible new tool for manipulating transgenic DNA in vivo.

Original languageEnglish (US)
Title of host publicationJournal of Biological Engineering
Volume2
DOIs
StatePublished - May 20 2008
Externally publishedYes

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Bacteria
DNA
Escherichia coli
Molecular Computers
Cell Engineering
Tetracycline Resistance
Recombinases
Salmonella
Salmonella typhimurium
Antibiotics
Genetic Recombination
Sorting
Plasmids
Demonstrations
Anti-Bacterial Agents
Cells
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Biomedical Engineering
  • Environmental Engineering
  • Cell Biology
  • Molecular Biology

Cite this

Haynes, K., Broderick, M. L., Brown, A. D., Butner, T. L., Dickson, J. O., Harden, W. L., ... Poet, J. L. (2008). Engineering bacteria to solve the Burnt Pancake Problem. In Journal of Biological Engineering (Vol. 2). [8] https://doi.org/10.1186/1754-1611-2-8

Engineering bacteria to solve the Burnt Pancake Problem. / Haynes, Karmella; Broderick, Marian L.; Brown, Adam D.; Butner, Trevor L.; Dickson, James O.; Harden, W. Lance; Heard, Lane H.; Jessen, Eric L.; Malloy, Kelly J.; Ogden, Brad J.; Rosemond, Sabriya; Simpson, Samantha; Zwack, Erin; Campbell, A. Malcolm; Eckdahl, Todd T.; Heyer, Laurie J.; Poet, Jeffrey L.

Journal of Biological Engineering. Vol. 2 2008. 8.

Research output: Chapter in Book/Report/Conference proceedingChapter

Haynes, K, Broderick, ML, Brown, AD, Butner, TL, Dickson, JO, Harden, WL, Heard, LH, Jessen, EL, Malloy, KJ, Ogden, BJ, Rosemond, S, Simpson, S, Zwack, E, Campbell, AM, Eckdahl, TT, Heyer, LJ & Poet, JL 2008, Engineering bacteria to solve the Burnt Pancake Problem. in Journal of Biological Engineering. vol. 2, 8. https://doi.org/10.1186/1754-1611-2-8
Haynes K, Broderick ML, Brown AD, Butner TL, Dickson JO, Harden WL et al. Engineering bacteria to solve the Burnt Pancake Problem. In Journal of Biological Engineering. Vol. 2. 2008. 8 https://doi.org/10.1186/1754-1611-2-8
Haynes, Karmella ; Broderick, Marian L. ; Brown, Adam D. ; Butner, Trevor L. ; Dickson, James O. ; Harden, W. Lance ; Heard, Lane H. ; Jessen, Eric L. ; Malloy, Kelly J. ; Ogden, Brad J. ; Rosemond, Sabriya ; Simpson, Samantha ; Zwack, Erin ; Campbell, A. Malcolm ; Eckdahl, Todd T. ; Heyer, Laurie J. ; Poet, Jeffrey L. / Engineering bacteria to solve the Burnt Pancake Problem. Journal of Biological Engineering. Vol. 2 2008.
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T1 - Engineering bacteria to solve the Burnt Pancake Problem

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AU - Broderick, Marian L.

AU - Brown, Adam D.

AU - Butner, Trevor L.

AU - Dickson, James O.

AU - Harden, W. Lance

AU - Heard, Lane H.

AU - Jessen, Eric L.

AU - Malloy, Kelly J.

AU - Ogden, Brad J.

AU - Rosemond, Sabriya

AU - Simpson, Samantha

AU - Zwack, Erin

AU - Campbell, A. Malcolm

AU - Eckdahl, Todd T.

AU - Heyer, Laurie J.

AU - Poet, Jeffrey L.

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