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Stanford CS 374 - Transforming cells into automata

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Slide 1Slide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29CS 374, Algorithms in Biology. Florian BuronTransforming cells into automata•Genetic Circuit Building Blocks for Cellular Computation (Gardner, Cantor and Collins)•Construction of a Genetic Toggle Switch in Escherichia Coli (Ron Weiss, Basu, Hooshangi, Kalmbach, Karig, Mehreja, Netravali)From biology to automata01010110001Protein A, etcInputcomputationProcessor,TransistorsDNAResult01000010001Protein B, etc.Biologic Computers and Robots…Applications:•Drug and biomaterial production and creation.•Programmed therapeutics.•Embedded intelligence in materials.•Environmental sensing and effecting.•Nanoscale fabrication.Promoters•Promoters are sequences in the DNA just upstream of transcripts that define the sites of initiation.•The role of the promoter is to attract RNA polymerase to the correct start site so transcription can be initiated.•Repressors or Activators can decrease or increase this attraction.5’Promoter3’Basic InverterImproved InverterdimereImproved InverterNAND operatorWe are kind of done!!!•With the NAND and the negation you can build a computer!•What about the implies operator?•A => B  not(A) or B  not(A and not(B))Implies operatorAnd operatorToggle switchToggle switchCircuit DesignHow do we choose the right proteins, inducers, etc?•Rational Design (simulator)•Directed EvolutionRational designRational designRational designRational designDirected evolution•Optimizing circuit performance is quite labor intensive…•Advantage of biological system: ability to evolve and be optimized under the pressure of natural and artificial selection.•=> directed evolution: random mutation in specific region.Directed evolutionDirected Evolution•Results:–Evolved mutant adjust the kinetic characteristics of the genetic network to produce the right behavior.–Produce effective amino acid substitution that would have been hard to develop rationally!–Ultimately, combining both approach should lead to the best solutions.Cell to cell communicationCell to cell communicationCell to cell communicationDecoding 2 incoming signalsDecoding 2 incoming signals:Concentration band detectorConclusion•Ability to program cell to do what we want (command the production of molecules).•Starting to understand and predict such process (simulator).•Directed evolution.•Still one main problems: biology is stochastic (reliability, accuracy,


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Stanford CS 374 - Transforming cells into automata

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