Genetic coupling across space and time

In many respects, bacteria are an ideal design platform for synthetic biology. They are small, extremely hardy, inexpensive to maintain, reproduce quickly, and comprise a vast array of species with unique properties. An expanding future landscape of integrated synthetic biology will use the native networks of diverse microbial species in concert with our own engineered gene circuits. In this talk, I will discuss two engineered gene circuits that incorporate host signaling machineries to communicate over large spaces and within short times.

I will first describe an LCD-like array of colony “biopixels” that collectively report the concentration of a target compound with a frequency-encoded signal[1]. These synchronous oscillations are maintained across populations as large as 13,000 colonies over centimeter length scales. Multi-scale coordination is achieved by layering 2 modes of communication – local quorum sensing and global redox signaling that utilizes the native aerobic response network.

I will then describe how we use protease competition to engineer rapid and tunable coupling of genetic circuits [2]. We characterize coupling delay times that are more than an order of magnitude faster than standard transcription-factor based coupling methods (less than one minute compared with ∼20-40 minutes). We use this mechanism as a platform to couple genetic clocks then show how the coupled clock network can be used to encode independent environmental inputs into a single time series output, thus enabling the possibility of frequency multiplexing in a genetic circuit context.

1. Prindle, A., et al., A sensing array of radically coupled genetic 'biopixels'. Nature, 2012. 481(7379): p. 39-44.
2. Prindle, A., et al., Rapid and tunable post-translational coupling of genetic circuits. Nature (in press), 2014.