Synthetic Biology is a field that is changing both how we understand and engineer biology.  Instead of adding/deleting one gene at a time the way we've done using genetic engineering techniques for 30 years, we are learning how to manipulate collections of genes to program entirely new behaviors in organisms that they do not normally do.  These new behaviors could be the engineered production of fuels or medicines, or the ability to act as biosensors that detect different environmental conditions or treat disease.

My Ph.D. mainly focused on developing a way to engineer bacteria to produce synchronized dynamic behavior across a population of cells.  Up until this point, most work had focused on engineering single cells, but coordinated behavior, although quite common in nature, is challenging to genetically program in the lab from the bottom-up.  To do this, we hijacked a genetic system called 'quorum sensing' from naturally occurring bacteria, which they use to communicate with one another and trigger behaviors such as virulence and biofilm development.  Putting together pieces of DNA to encode this behavior we built the design (below) and created microscope 'movies' of bacteria transformed with this system.   

Below is a schematic of how we wired these different genes together.  There is more scientific detail in the captions, but for the average reader, this Nature produced video gives the best introduction to how we synchronized bacterial behaviors.

By synchronising our clocks, we can coordinate our activities with people around the world. Now, scientists have engineered bacteria to synchronise their molecular timekeepers, creating the stunning fluorescent waves you see in this video.

Synchronized genetic clock circuit. The luxI promoter drives production of the luxI, aiiA and yemGFP genes in three identical transcriptional modules. LuxI enzymatically produces a small molecule AHL, which can diffuse outside of the cell membrane and into neighbouring cells, activating the luxI promoter. AiiA negatively regulates the circuit by acting as an effective protease for AHL

Synchronized genetic clock circuit. The luxI promoter drives production of the luxI, aiiA and yemGFP genes in three identical transcriptional modules. LuxI enzymatically produces a small molecule AHL, which can diffuse outside of the cell membrane and into neighbouring cells, activating the luxI promoter. AiiA negatively regulates the circuit by acting as an effective protease for AHL

Timelapse of a population of synchronized bacteria.  Fluorescence slices of a typical experimental run demonstrate synchronization of oscillations in a population of E. coli residing in the microfluidic device (Supplementary Movie 1). Inset in the first snapshot is a ×100 magnification of cells.  To see a movie of this sequence, see below.  

Timelapse of a population of synchronized bacteria.  Fluorescence slices of a typical experimental run demonstrate synchronization of oscillations in a population of E. coli residing in the microfluidic device (Supplementary Movie 1). Inset in the first snapshot is a ×100 magnification of cells.  To see a movie of this sequence, see below.  

Synchronized genetic clock circuit in bacteria

 

Arthur Prindle, a graduate student at UCSD, extended this further by synchronizing not just individual bacteria, but colonies of bacteria to each other via gas communication (see Prindle Nature 2011 or read more here). In this movie below, each little square represents a few thousand of bacteria that you saw in the movies above.  This was a significant advance, not only because the scale of synchronization was increased, but also because these bacteria were programmed to flash at different frequencies according to how much Arsenic they sensed in their growth chambers.  Thus, they could act as biosensors to warn against groundwater contamination from harmful chemicals.

Researchers Create Living 'Neon Signs' Composed of Millions of Glowing Bacteria

 

Art+Outreach

In addition to the interesting visual science behind our work, I found that these microscopic movies were engaging to a wide audience and I started using them for science-outreach at demos, museums, and presentations.  Below is a compilation of these movies in different forms.  

If you want to use or see a playlist of these videos, check out this Youtube playlist.   We've used these at a variety of different demos and events.  

As part of this project we developed an image called The Supernova.  To read more about this click here.