Bacterial computing

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BacterialComputingUndergraduate students find that agenetically engineered machine cansolve Hamiltonian Path Problems.By Jeffrey L. Poet, A. Malcolm Campbell,Todd T. Eckdahl, and Laurie J. HeyerDOI: 10.1145/1836543.1836550Amultidisciplinary group of students from MissouriWestern State University and Davidson College (underour mentorship) recently designed and constructed aproof-of-concept experiment to solve a HamiltonianPath Problem inside live bacteria. The students workedwithin a new field called synthetic biology, which seeks toapply engineering principles (including standardization,modularity, and abstraction), mathematical modeling, andmolecular biology techniques to build biological machinesto perform functions with applications in medicine, theenvironment, energy, and technology.A Hamiltonian path is a sequenceof directed edges, in a directed graph,that start at one node and end at anothernode while visiting all nodesexactly once. A directed graph is a setof nodes with directed edges betweensome pairs of nodes. A HamiltonianPath Problem (HPP) asks, for a givendirected graph and specified beginningand ending nodes, does there exista Hamiltonian path in the graph?For example, the graph in Figure 1 hasa unique Hamiltonian path beginningat node 1 and ending at node 5.In 1994, Leonard Adleman (who putthe A in RSA cryptography) published aseminal paper on DNA computing. Thearticle [1] described Adleman’s in vitroexperiment in which the edges of thegraph of Figure 1 were represented bystrands of DNA with the property thateach strand could only attach itself tocertain other strands.DNA is composed of four nucleotides,represented by A, T, G, and C.In double-stranded DNA, an A on onestrand always pairs with a T on theother strand, and similarly, a G on onestrand always pairs with a C on the other.These A-T and G-C interactions arecalled Watson-Crick base pairing.Adleman constructed single-strandedsegments of DNA so that as thesesegments of DNA “found each other”in the test tube, compatible segmentsassembled by base pairing to form longerand longer pieces of double-strandedDNA. At the end of the binding step,“A single E. colibacterium willreplicate itselfapproximatelyevery 30 minutes.Growing a bacteriumovernight resultsin approximatelya billion identical,independentbiologicalprocessors.”X R D S • F A L L 2 0 1 0 • V O L . 17 • N O . 1 11
Bacterial ComputingFigure 1: A directed graph with seven nodes, 14 directed edges, and a unique Hamiltonian path is shown. Leonard Adleman inthe 1990s used in vitro DNA techniques to find the unique Hamiltonian path.2341576“Synthetic biologyis a natural fit formultidisciplinaryresearch forundergraduatestudents. TheiGEM communityprovides a supportiveenvironment forteams wishing toengage in research.”Adleman checked segments of the correctlength for representation of eachnode and found some segments thatcorresponded to the unique Hamiltonianpath of the directed graph in Figure1. Adelman’s breakthrough experimentdemonstrated the application ofbiological molecules to solve a computationalproblem.In trying to solve the problem in anew way, the students took a differentapproach. The team, composed of studentsfrom two campuses, as well asfaculty from the mathematics and biologydepartments, designed and constructeda proof-of-concept experimentto solve a HPP inside live bacteria.The team participated in the InternationalGenetically Engineered Machines(iGEM) competition. iGEM beganin 2004 with five teams from theU.S. In 2010, there were more than 130teams from North America, Latin America,Europe, Asia, and Africa that sharedinformation and resources in an effortto advance the field of synthetic biology.The iGEM community specifically targetsundergraduate students becauseof their creativity and enthusiasm. Eachyear iGEM students design, build, andtest synthetic biology projects with variedapplications and present them atthe annual iGEM Jamboree held at MassachusettsInstitute of Technology.HURDLES TO CREATINGA BACTERIAL COMPUTERDesigning and constructing a bacterialcomputer to solve any math problempresents several distinct challenges.First, how will the components of theproblem be encoded into the DNA of abacterium? Second, how will the informationbe manipulated (a necessarycomponent for computation)? Finally,how will the results of the computationbe “displayed”?The students addressed each ofthese challenges to solve the HPP. Theused in this design used living E. colito find the solution to the HPP, and isshown in Figure 2.12X R D S • F A L L 2 0 1 0 • V O L . 17 • N O . 1
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