Jeff Hasty, Ph.D.

To make a new kind of display, researchers have engineered bacteria to be brighter.

The University of California at San Diego last month detailed the latest advances toward making a lighting system powered by genetically engineered e. coli bacteria.

Bioengineers insert a protein that causes the bacteria to fluoresce. Assembled in colonies, these bacteria act as a light source, like the pixel on a screen. About 500 individual bacteria are assembled into colonies, or “biopixels.”

Those biopixels were engineered as components in larger circuits to make a display with as many as 13,000 biopixels.

The hope is that these biological circuits can be used as sensors for pollutants or other hazardous materials. In its tests, biopixels were able to detect arsenic by blinking on and off in unison.

One of the biggest technical challenges is to coordinate blinking across so many individual bacteria. Researchers designed their microfluidic chips so that gas is passed between colonies to synchronize blinking.

In five years, the technology could be used for a long-lasting and cheap environmental sensor, said Jeff Hasty, a professor at UC San Diego’s Division of Biological Sciences and BioCircuits Institute who headed the research. “These kinds of living sensors are intriguing as they can serve to continuously monitor a given sample over long periods of time, whereas most detection kits are used for a one-time measurement,” Hasty said in a statement.

The biological sensor shows the presence and levels of arsenic through the frequency of the oscillations of the cells’ pattern of blinking

Just in time for the Christmas season are cells that resemble Christmas twinkle lights. University of California – San Diego scientists have created neon signs made of blinking bacterial cells, which could eventually be used to detect toxic substances and their concentrations.

The research, which was led by Jeff Hasty, professor of biology and bioengineering at UC San Diego, involves binding a fluorescent protein to the biological clocks of the bacterial cells, then synchronizing these biological clocks. This leads to the simultaneous blinking of the glowing cells.

The researchers created the neon signs of bacteria by tapping into their natural form of communication amongst each other. Bacterial cells are synchronized via quorum sensing, where they relay molecules between one another to initiate and synchronize certain behaviors. However, using this method to synchronize millions of bacteria from different colonies is challenging.

University of California San Diego scientists who are exploring how to program cells to perform machine-like tasks such as monitoring the environment found a way to make lowly bacteria glow, blink in unison and spell out the school’s initials.

The bacteria were turned into “blinking light bulbs,” as the university describes it, using a technique that’s also allowed researchers to program the single-cell organisms to detect low levels of arsenic, an element that can be damaging to the environment.

“These kinds of living sensors are intriguing as they can serve to continuously monitor a given sample over long periods of time, whereas most detection kits are used for a one-time measurement,” UCSD biologist Jeff Hasty says in a release announcing the advance.

These microfluidic chips contain about 500 blinking bacterial colonies or biopixels. — UCSD
Hasty says that a fluorescent protein was added to the biological clock of each bacteria through genetic engineering, giving the organisms the ability to glow.

“We … engineered bacteria to blink on and off by inserting genes that regulate each other such that you get rhythms,” Hasty said. “Each cell oscillates on its own, so you have the blinking phase of one cell unrelated to its neighbors.

In an example of life imitating art, biologists and bioengineers at UC San Diego have created a living neon sign composed of millions of bacterial cells that periodically fluoresce in unison like blinking light bulbs.

Their achievement, detailed in this week’s advance online issue of the journal Nature, involved attaching a fluorescent protein to the biological clocks of the bacteria, synchronizing the clocks of the thousands of bacteria within a colony, then synchronizing thousands of the blinking bacterial colonies to glow on and off in unison.

A little bit of art with a lot more bioengineering, the flashing bacterial signs are not only a visual display of how researchers in the new field of synthetic biology can engineer living cells like machines, but will likely lead to some real-life applications.

Using the same method to create the flashing signs, the researchers engineered a simple bacterial sensor capable of detecting low levels of arsenic. In this biological sensor, decreases in the frequency of the oscillations of the cells’ blinking pattern indicate the presence and amount of the arsenic poison.

Biologists have long known that organisms from bacteria to humans use the 24 hour cycle of light and darkness to set their biological clocks. But exactly how these clocks are synchronized at the molecular level to perform the interactions within a population of cells that depend on the precise timing of circadian rhythms is less well understood.

To better understand that process, biologists and bioengineers at UC San Diego created a model biological system consisting of glowing, blinking E. coli bacteria. This simple circadian system, the researchers report in the September 2 issue of Science, allowed them to study in detail how a population of cells synchronizes their biological clocks and enabled the researchers for the first time to describe this process mathematically.

“The cells in our bodies are entrained, or synchronized, by light and would drift out of phase if not for sunlight,” said Jeff Hasty, a professor of biology and bioengineering at UC San Diego who headed the research team. “But understanding the phenomenon of entrainment has been difficult because it’s difficult to make measurements. The dynamics of the process involve many components and it’s tricky to precisely characterize how it works.  Synthetic biology provides an excellent tool for reducing the complexity of such systems in order to quantitatively understand them from the ground up. It’s reductionism at its finest.”