1. CS 374, Algorithms in Biology. Florian Buron Transforming 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)

2. From biology to automata 01010110001 Protein A, etc Input computation Processor, Transistors DNA Result 01000010001 Protein B, etc.

3. Biologic Computers and Robots…

4. Applications: Drug and biomaterial production and creation. Programmed therapeutics. Embedded intelligence in materials. Environmental sensing and effecting. Nanoscale fabrication.

6. 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’ Promoter 3’

7. Basic Inverter

8. Improved Inverter dimere

9. Improved Inverter

10. NAND operator

11. We 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))

12. Implies operator

13. And operator

14. Toggle switch

16. Circuit Design How do we choose the right proteins, inducers, etc? Rational Design (simulator) Directed Evolution

17. Rational design

21. Directed 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.

22. Directed evolution

23. Directed 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.

24. Cell to cell communication

27. Decoding 2 incoming signals Decoding 2 incoming signals:

28. Concentration band detector

29. Conclusion 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, etc.)