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Oscillatory Systems. Jesse Wu 2009-03-18. Outline. What is an oscillator? Types of oscillators Oscillator related things to think about. What is an oscillator?. Something which its expression value is based on a time period. Implementation Within cell oscillator:
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Oscillatory Systems Jesse Wu 2009-03-18
Outline • What is an oscillator? • Types of oscillators • Oscillator related things to think about
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
Three component oscillator • Repressilator • Elowitz et al (2000), Nature. • The original synthetic oscillator that started it all. • Cyanoxilator • NYMU-Taipei08
Three component oscillator - Repressilator PB C PC A Pa B Pa GFP
Three component oscillator - Cyanoxilator • A natural oscillator occurring in Cyanobacteria. • Has a period of 14 - 60 hrs. Oscillator KaiA P P Output KaiB P SasA P RpaA P P P P P P P P P KaiC P P P P P 6
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 Pa A
Two component oscillator - Reloxilator • One positive feedback loop + one negative feedback loop • Also mostly depends upon protease degradation rate PRE GFP GFP The Reporter PRE CII CII PRE HflB HflB The Oscillator
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
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.
Reloxilator: An oscillator including a synchronize and tuner PRE GFP GFP PRE CII The Reporter CII PLUX CII PRE HflB R+AHL HflB PLAC LuxR The Oscillator R AHL PLAC CIIIC CIIIC PRE LuxI L The Tuner The Synchronizer
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.