20.109(F10):Variable Genetic Timer

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.

http://www.seoish.com/wp-content/uploads/2009/05/stopwatch.png

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

=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


 * A cell-intrinsic timer that operates during oligodendrocyte development. Béatrice Durand, Martin Raff


 * Clocks regulating developmental processes. Laboratoire de Génétique et de Physiologie du Développement (LGPD), CNRS-INSERM-Université de la Méditerranée-AP de Marseille, France


 * Hope A Johnson, Anubhuthi Goel, Dean V Buonomano. Neural dynamics of in vitro cortical networks reflects experienced temporal patterns. Nature Neuroscience, 2010;

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:
 * T9002: Receiver Device
 * S03623: Sender Device

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.