20.109(F10):Variable Genetic Timer

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The goal of a variable genetic timer is to drive a time-delayed transcriptional response to a given input, where the delay is gain is proportional to a particular chemical input. The emphasis here is on providing a circuit that delays across a tunable range of delay values rather than discrete steps.


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20.109(F10)Team Green: Cory L. && Shikha K.

Contents

Background Information

Similar Systems

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796999/

Artificial Gene Networks -- Assembly of protein modification and transcription-control components to design a synthetic mammalian time-delay circuit that emulates an electronic switchboard with sequential wiring of diodes, capacitors/resistors/transistors by Biotin-triggered transgene expression (nontoxic, vitamin H) -quorum sensing cross talk -modulate toll-like signaling pathways -adjust circadian clock (delayed phosphorylation-dependent degredation or or differential ubiquitinylation)


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1386718/


Natural Systems

Lots of natural timers include both natural cell division regulation

Synthetic Systems

RTC Counter

Riboregulated transcriptional cascade. A step loop structure blocks the RBS and prevents transcription. Pulses of Arabinose inhibit this loop and allow the next stage in the cascade to begin.

Ref: Synthetic Gene Networks That Count. Ari E. Friedland, Timothy K. Lu, Xiao Wang, David Shi, George Church, and James J. Collins. Science 29 May 2009: 324 (5931), 1199-1202.

Switching Consortium

Slow accumulation of AHL triggers the activation threshold, and tunability is achieved via modification of receiver sensitivity or producer output.

Implementation: iGEM 2008 Chiba

Parts:

Implementation: 2009 iGEM NCTU Formosa

Repressilator

Not really a "timer" rather than a "time keeper," but I'll keep this here for completeness sake.

Ref: A synthetic oscillatory network of transcriptional regulators. Elowitz MB, Leibler S. Nature 20 Jan 2000;403(6767):335-8.

Resource Exhaustion

Closer to a tunable timer, but only one time use. System is seeded with a certain metabolite to a given concentration and the system is activated when the metabolite is used up.

Ref: 2007 Missouri

Recombination Counter

Integrase excises a terminator sequence which blocks the output. Can be cascaded for a multi-step one-time-use discrete timer.

Ref: iGEM 2010 Paris

Ideas

  • A chemical input causes a proportional buildup of an antagonist molecule which must be slowly degraded at some constant rate. Circuit then fires once the system is cleared of the antagonist.
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