Solving a Hamiltonian Path Problem with a bacterial computer

Baumgardner, Jordan; Acker, Karen P.; Adefuye, Oyinade; Crowley, Samuel T.; DeLoache, Will; Dickson, James O; Heard, Lane H; Martens, Andrew T.; Morton, Nickolaus; Ritter, Michelle; Shoecraft, Amber; Treece, Jessica; Unzicker, Matthew R.; Valencia, A.; Waters, Mike; Campbell, A. Malcolm; Heyer, Laurie J.; Poet, Jeffrey L.; Eckdahl, Todd T.

doi:10.1186/1754-1611-3-11

Cited by 61 publications

(44 citation statements)

References 21 publications

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“…Synthetic systems have demonstrated the feasibility of flipping multiple overlapping regions flanked by a series of hix sites (Ham et al 2008;Haynes et al 2008;Baumgardner et al 2009). The flipping reaction appears to operate efficiently over inter-hix distances ranging from 100 bases to 5 kb (Ham et al 2008 and references therein), and the enhancer sequence can function several kilobases from these sites (Moskowitz et al 1991).…”

Section: Resultsmentioning

confidence: 99%

“…The proteins Q and R might be enzymes in a double auxotroph strain; alternatively, they might confer resistance when cells are grown in a medium containing two different antibiotics. Finally, it has been shown that a hixC site can be inserted in the coding region of the green fluorescent protein (GFP) gene, allowing it to be reversibly ''split'' by DNA inversion events (Baumgardner et al 2009). The utility of this unusual property will become clear as our discussion proceeds.…”

Section: Resultsmentioning

confidence: 99%

“…The Hin/ hix system lends itself to the modular engineering approach advocated by the synthetic biology community (Andrianantoandro et al 2006;Boyle and Silver 2009;Purnick and Weiss 2009). The Hin protein along with an artificial hixC site (Lim et al 1992) was recently used in three synthetic genetic constructs: a multistate genetic memory device (Ham et al 2008) and two systems designed to solve combinatorial mathematics problems (Haynes et al 2008;Baumgardner et al 2009). We propose that recombinase-based synthetic constructs such as these can be used to engineer regulated microbial consortia.…”

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confidence: 99%

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Flipping DNA to Generate and Regulate Microbial Consortia

Ramadas

Thattai

2010

Genetics

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Communities of interdependent microbes, found in diverse natural contexts, have recently attracted the attention of bioengineers. Such consortia have potential applications in biosynthesis, with metabolic tasks distributed over several phenotypes, and in live-cell microbicide therapies where phenotypic diversity might aid in immune evasion. Here we investigate one route to generate synthetic microbial consortia and to regulate their phenotypic diversity, through programmed genetic interconversions. In our theoretical model, genotypes involve ordered combinations of DNA elements representing promoters, proteincoding genes, and transcription terminators; genotypic interconversions are driven by a recombinase enzyme that inverts DNA segments; and selectable phenotypes correspond to distinct patterns of gene expression. We analyze the microbial population as it evolves along a graph whose nodes are distinct genotypes and whose edges are interconversions. We show that the steady-state proportion of each genotype depends on its own growth advantage, as well as on its connectivity to other genotypes. Multiple phenotypes with identical or distinct growth rates can be indefinitely maintained in the population, while their proportion can be regulated by varying the rate of DNA flipping. Recombinase-based synthetic constructs have already been implemented; the graph-theoretic framework developed here will be useful in adapting them to generate microbial consortia.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Flipping DNA to Generate and Regulate Microbial Consortia

Ramadas

Thattai

2010

Genetics

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“…Since then, several small scale systems have been constructed, either in the lab or in simulation (Amos 2004). Other examples of in vitro implementations of cellular computing systems include band detectors, coupled oscillations (Basu et al 2004(Basu et al , 2005 and, more recently, a solution to the three vertices Hamiltonian path problem (Baumgardner et al 2009). …”

Section: Introductionmentioning

confidence: 99%

A computational study of liposome logic: towards cellular computing from the bottom up

et al. 2010

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In this paper we propose a new bottom-up approach to cellular computing, in which computational chemical processes are encapsulated within liposomes. This ''liposome logic'' approach (also called vesicle computing) makes use of supra-molecular chemistry constructs, e.g. protocells, chells, etc. as minimal cellular platforms to which logical functionality can be added. Modeling and simulations feature prominently in ''top-down'' synthetic biology, particularly in the specification, design and implementation of logic circuits through bacterial genome reengineering. The second contribution in this paper is the demonstration of a novel set of tools for the specification, modelling and analysis of ''bottom-up'' liposome logic. In particular, simulation and modelling techniques are used to analyse some example liposome logic designs, ranging from relatively simple NOT gates and NAND gates to SR-Latches, D Flip-Flops all the way to 3 bit ripple counters. The approach we propose consists of specifying, by means of P systems, gene regulatory network-like systems operating inside proto-membranes. This P systems specification can be automatically translated and executed through a multiscaled pipeline composed of dissipative particle dynamics (DPD) simulator and Gillespie's stochastic simulation algorithm (SSA). Finally, model selection and analysis can be performed through a model checking phase. This is the first paper we are aware of that brings to bear formal specifications, DPD, SSA and model checking to the problem of modeling target computational functionality in protocells. Potential chemical routes for the laboratory implementation of these simulations are also discussed thus for the first time suggesting a potentially realistic physiochemical implementation for membrane computing from the bottom-up.

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“…Bacterial computers provide a unique alternative technology to silicon computers. Cellular computers have the advantage of exhibiting enormous parallel computing capabilities, intercellular communication, ability to interface with the biological world, and reusability 5,6 . Computing efficiency may result from the use of single analog logic gates in a population of bacterial computers, as opposed to the thousands of gates required in digital processes used by conventional computers 7 .…”

Section: Introductionmentioning

confidence: 99%

Bacterial Hash Function Using DNA-Based XOR Logic Reveals Unexpected Behavior of the LuxR Promoter

Pearson¹,

Lau²,

Allen³

et al. 2011

Interdisciplinary Bio Central

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SYNOPSIS Introduction:Hash functions are computer algorithms that protect information and secure transactions. In response to the NIST"s "International Call for Hash Function", we developed a biological hash function using the computing capabilities of bacteria. We designed a DNA-based XOR logic gate that allows bacterial colonies arranged in a series on an agar plate to perform hash function calculations. Results and Discussion: In order to provide each colony with adequate time to process inputs and perform XOR logic, we designed and successfully demonstrated a system for time-delayed bacterial growth. Our system is based on the diffusion of ß -lactamase, resulting in destruction of ampicillin. Our DNA-based XOR logic gate design is based on the opposition of two promoters. Our results showed that Plux and POmpC functioned as expected individually, but Plux did not behave as expected in the XOR construct. Our data showed that, contrary to literature reports, the Plux promoter is bidirectional. In the absence of the 3OC6 inducer, the LuxR activator can bind to the Plux promoter and induce backwards transcription. Conclusion and Prospects: Our system of time delayed bacterial growth allows for the successive processing of a bacterial hash function, and is expected to have utility in other synthetic biology applications. While testing our DNA-based XOR logic gate, we uncovered a novel function of Plux. In the absence of autoinducer 3OC6, LuxR binds to Plux and activates backwards transcription. This result advances basic research and has important implications for the widespread use of the Plux promoter.

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Solving a Hamiltonian Path Problem with a bacterial computer

Cited by 61 publications

References 21 publications

Flipping DNA to Generate and Regulate Microbial Consortia

Flipping DNA to Generate and Regulate Microbial Consortia

A computational study of liposome logic: towards cellular computing from the bottom up

Bacterial Hash Function Using DNA-Based XOR Logic Reveals Unexpected Behavior of the LuxR Promoter

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