Thousands of fluorescent E. coli bacteria make up a biopixel. Photos/Hasty Lab, UC San Diego
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.
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.
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.
bacteria are sensitive to many kinds of environmental pollutants and
organisms, the scientists believe this approach could be also used to
design low cost bacterial biosensors capable of detecting an array of
heavy metal pollutants and disease-causing organisms. And because the
senor is composed of living organisms, it can respond to changes in the
presence or amount of the toxins over time unlike many chemical sensors.
Tiny microfluidic chips allow the researchers to synchronize the bacteria to fluoresce or blink in unison.
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,” said Jeff
Hasty, a professor of biology and bioengineering at UC San Diego who
headed the research team in the university’s Division of Biological
Sciences and BioCircuits Institute. “Because the bacteria respond in
different ways to different concentrations by varying the frequency of
their blinking pattern, they can provide a continual update on how
dangerous a toxin or pathogen is at any one time.”
development illustrates how basic, quantitative knowledge of cellular
circuitry can be applied to the new discipline of synthetic biology,”
said James Anderson, who oversees synthetic biology grants at the
National Institutes of Health’s National Institute of General Medical
Sciences, which partially funded the research. “By laying the foundation
for the development of new devices for detecting harmful substances or
pathogens, Dr. Hasty’s new sensor points the way toward translation of
synthetic biology research into technology for improving human health.”
development of the techniques to make the sensor and the flashing
display built on the work of scientists in the Division of Biological
Sciences and School of Engineering, which they published in two previous
papers over the past four years. In the first paper, the scientists
demonstrated how they had developed a way to construct a robust and
tunable biological clock to produce flashing, glowing bacteria. In the
second paper, published in 2010, the researchers showed how they
designed and constructed a network, based on a communication mechanism
employed by bacteria, that enabled them to synchronize all of the
biological clocks within a bacterial colony so that thousands of
bacteria would blink on and off in unison.
bacteria species are known to communicate by a mechanism known as
quorum sensing, that is, relaying between them small molecules to
trigger and coordinate various behaviors,” said Hasty, explaining how
the synchronization works within a bacterial colony. “Other bacteria are
known to disrupt this communication mechanism by degrading these relay
the researchers found the same method couldn’t be used to
instantaneously synchronize millions of bacteria from thousands of
The smaller chips like this one contain about 500 blinking bacterial colonies or biopixels. The larger chips contain about 13,000 biopixels.
you have a bunch of cells oscillating, the signal propagation time is
too long to instantaneously synchronize 60 million other cells via
quorum sensing,” said Hasty. But the scientists discovered that each of
the colonies emit gases that, when shared among the thousands of other
colonies within a specially designed microfluidic chip, can synchronize
all of the millions of bacteria in the chip.
colonies are synchronized via the gas signal, but the cells are
synchronized via quorum sensing. The coupling is synergistic in the
sense that the large, yet local, quorum communication is necessary to
generate a large enough signal to drive the coupling via gas exchange,”
students Arthur Prindle, Phillip Samayoa and Ivan Razinkov designed the
microfluidic chips, which for the largest ones, contain 50 to 60
million bacterial cells and are about the size of a paper clip or a
microscope cover slip. The smaller microfluidic chips, which contain
approximately 2.5 million cells, are about a tenth of the size of the
of the blinking bacterial colonies comprise what the researchers call a
“biopixel,” an individual point of light much like the pixels on a
computer monitor or television screen. The larger microfluidic chips
contain about 13,000 biopixels, while the smaller chips contain about
said he believes that within five years, a small hand-held sensor could
be developed that would take readings of the oscillations from the
bacteria on disposable microfluidic chips to determine the presence and
concentrations of various toxic substances and disease-causing organisms
in the field.
Other UC San Diego scientists involved in the discovery were Tal Danino and Lev Tsimring.
UC San Diego Technology Transfer Office has filed a patent application
on the Hasty group’s invention. Anyone with commercial interest in the
research or application should contact Eric Gosink, senior licensing
officer, at email@example.com.