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Download Metabolic Wiring We are introducing a newly discovered cell
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Edinburgh iGEM 2014 Philip Davies, Cesar Pumar Garcia, Carrie Pickering, Anna Stikane, Elize Petrovska, Sam Ireland , Chiara Asselborn, Rikki Guy, Yuma Shino, Metabolic Wiring Iterated Prisoner’s Dilemma We are introducing a newly discovered cell-cell communication method to iGEM, called metabolic wiring. This uses intermediate metabolites of a pathway as the signalling molecules. Our aim is to establish this new orthogonal signalling mechanism for the synthetic biology community. To demonstrate its potential, we are using MW to build a complex circuit in the Iterated Prisoner’s Dilemma game. We intend to make an interactive demonstration of biological circuits, by designing bacteria that can play a game both against each other and against humans. In the game, Iterated Prisoner’s Dilemma (IPD), players have the choice to cooperate or betray the other player for a varying reward. We have recreated four simple strategies from logic gates. Cooperate Cooperate £10 Each Betray Regulatory protein Reaction Gene PobR p-Hydroxybenzoate into protocatechuate pobA PcaU Protocatechuate into acetyl CoA and succinyl Coa pcaIJFBDKCHG BenR Benozoate into catechol BenABC PcaV Catechol (or protocatechuate) into acetyl CoA pcaH £5 Each Betray Betray Cooperate £0 £20 How to play iterated prisoner’s dilemma against a bacterium 2. Bacteria show cooperate or defect 1. Tell the bacteria to choose 3. Wash away the signal Toggle switch based memory Circuits for Iterated Prisoner’s Dilemma Grim Trigger Behaviour Human's Choice Bacteria's Choice C C C C B C B glnG Output Betray e.g. RFP lacI Ptrc-2 PLtetO-1 tetR Output Cooperate e.g. GFP IF C Next is C IF C Next is C IF B Next is B Signal Betray lacY Tit for Tat Behaviour Human's Choice Bacteria's Choice C C B C B 4. Tell the bacteria what you chose Signal Cooperate lacI Output Betray e.g. RFP Recombinase/Repressor AND Output Betray Output Cooperate Signal Cooperate Signal Betray OR AND Output Cooperate e.g. GFP Tit for two Tat Behaviour Human's Choice Bacteria's Choice C C B C C Memory formation inducer IF B Next is B Tit for Tat Modelling and Software The two major aspects (population control and the prisoner’s dilemma) will require two different modelling techniques. The prisoner’s dilemma can partly be modelled as a logical circuit, but also requires a biological oscillator (to manage iterations), for which there are many pre-existing models available using sets of ordinary differential equations. There are many preexisting pieces of modelling software available to us, including the open-source Kappa Simulator, allowing for us to easily run full simulations of our models. Modelling will particularly important for determining the stability of the population control system. References: Silva-Rocha R and Lorenzo V. (2013). Engineering Multicellular Logic in Bacteria with Metabolic Wires. ACS Synthetic Biology. 3 (1), 204-209 Grim Trigger IF C Next is C IF B Next is B Tit for Two Tat Metabolic wiring: future applications One of the many future applications enabled by this technology, is a system for regulating the composition of a mixed culture. By using the population sizes of two strains as the inputs for regulating the growth of the third strain, we could theoretically achieve a steady state, where all three populations are present in the exact proportions that we define. In this figure, each strain is represented by AND gate, the output of which is its own population size.
