1. Oscillatory Systems Jesse Wu 2009-03-18

2. Outline What is an oscillator? Types of oscillators Oscillator related things to think about

3. What is an oscillator? Something which its expression value is based on a time period. Implementation Within cell oscillator: Three component oscillator Two component oscillator One component oscillator Other types of oscillators

4. Three component oscillator Repressilator Elowitz et al (2000), Nature. The original synthetic oscillator that started it all. Cyanoxilator NYMU-Taipei08

5. Three component oscillator - Repressilator PBPB CPCPC A PaPa B PaPa GFP

6. 6 Output KaiA KaiC Oscillator KaiB SasARpaA P P P P P P P P P P P P P P P P P P Three component oscillator - Cyanoxilator A natural oscillator occurring in Cyanobacteria. Has a period of 14 - 60 hrs.

7. One component oscillator Negative feedback loop. Sounds nice theoretically Modelling doesn’t produce great results Promoter immediately increases amount of X So time period depends mostly on degradation time of X Probably worse in reality PaPa A

8. Two component oscillator - Reloxilator One positive feedback loop + one negative feedback loop Also mostly depends upon protease degradation rate P RE CII P RE HflB CII HflB The Oscillator P RE GFP The Reporter

9. Other types of oscillators Cell cycle Expression based on cell cycle Cell population oscillator Expression based on number of cells in the immediate vicinity. Quorum sensing (Imperial07) Metabolic oscillator (Metabolator) An oscillator which has a whole pathway E.g. The TCA cycle

10. Oscillatory related things to think about In general: Host cell consideration  very important! Other factors which may affect the oscillatory expression Tuner: to be able to control the period of oscillation. For within-cell oscillators: Synchronizer: Synchronizes oscillations between different cells.

11. Reloxilator: An oscillator including a synchronize and tuner P RE CII P RE HflB P RE LuxI P LUX CII HflB L AHL P LAC CIIIC The Oscillator The TunerThe Synchronizer P RE GFP The Reporter P LAC LuxR R R+AHL

12. Summary Oscillators win, if they work. There are many types of oscillators. There are many related things to think about when designing an oscillator. Make sure you do modelling. Nothing is impossible. Just do it. Now.