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Programming Biological Cells

Programming Biological Cells. Ron Weiss, George Homsy, Radhika Nagpal Tom Knight, Gerald Sussman, Nick Papadakis MIT Artificial Intelligence Laboratory. Motivation. Goal: program biological cells Characteristics small ( E.coli : 1 x 2 m , 10 9 /ml) self replicating energy efficient

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Programming Biological Cells

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  1. Programming Biological Cells Ron Weiss, George Homsy, Radhika Nagpal Tom Knight, Gerald Sussman, Nick Papadakis MIT Artificial Intelligence Laboratory

  2. Motivation • Goal: program biological cells • Characteristics • small (E.coli: 1x2m , 109/ml) • self replicating • energy efficient • Potential applications • “smart” drugs / medicine • agriculture • embedded systems

  3. logic circuit high-level program genome microbial circuit compiler Approach • Building biological digital circuits • compute, connect gates, store values • High-level programming issues Outline:

  4. [A] [Z] [A] [Z] [A] [Z] = 0 = 1 = 1 = 0 Z A Compute: Biological Inverter • signal = protein concentration level • computation = protein production + decay

  5. Inverter Behavior • Simulation model based on l phage biochemistry [A] [ ] active gene [Z] time (x100 sec)

  6. Connect: Ring Oscillator • Connected gates show oscillation, phase shift [A] [B] [C] time (x100 sec)

  7. _ R = A _ S B _ [R] _ [S] [B] [A] Memory: RS Latch time (x100 sec)

  8. Microbial Circuit Design • Assigning proteins is hard. • BioSPICE: Simulate a colony of cells logic circuit genome microbial circuit compiler BioSPICE protein DB

  9. BioSPICE • Prototype protein level simulator • intracellular circuits, intercellular communication protein concentration cell Simulation snapshot

  10. High Level Programming • Requires a new paradigm • colonies are amorphous • cells multiply & die often • expose mechanisms cells can perform reliably • Microbial programming language • example: pattern generation using aggregated behavior

  11. Conclusions + Future Work • Biological digital gates are plausible • Now: • Implement digital gates in E. coli • Also: • Analyze robustness/sensitivity of gates • Construct a protein kinetics database • Study proteinprotein interactions for faster logic circuits

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