Sunday, May 21, 2006

"New bacterial communication lines by laboratory evolution of LuxR" - Frances Arnold

Let's make a new communication system by utilizing an existing communication system.

"I'm just the parts lady; I'm the one who has to sit there figure out how to define parts to... and so LuxR is my chosen substrate."

Novel idea for using signal pathways: predator-prey system, consensus consortium - something activates only when two cells are in proximity (i.e. in a biofilm).

Overview of Lux system:
V. fisheri synthase LuxI diffuses into medium, signal accumulates, binds to LuxR, activates gene transcription, turn on luciferase.

Here's some more information about LuxR and it's many cousins, which respond to a variety of acyl-homserine lactones.

The challenge is to evolve LuxR to respond to other signal molecules, multiplying the number of signalling pathways available to biological circuits.

Dual selection systems to evolve mutants (easy to make mutants, hard to find the ones that have the desired mutation; main principle of solution is to provide a selection pressure that only allows mutants with the desired solution to survive or to report themselves. Generalized dual selection system for maintaining specificity).

LuxR is modular, it is possible to recombine LuxR to respond different promoters, so in principle it should be possible to evolve new domain-swapped activators (why hasn't this worked before?)

Conclusion: "LuxR can give rise to a set of "standardized parts" for programmed cell-cell communications."

7-word summary of synth biology:
"Genome. Great story! Hard to write..."
Need a good editor. Evolution is one of the best! Massively parallel selection screens could be the "answer."

Collins et al nature biotech may or june

No comments: