Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

MIT team builds most complex synthetic biology circuit yet

10.10.2012
New sensor can detect four different molecules, could be used to program cells to precisely monitor their environments.

Using genes as interchangeable parts, synthetic biologists design cellular circuits that can perform new functions, such as sensing environmental conditions. However, the complexity that can be achieved in such circuits has been limited by a critical bottleneck: the difficulty in assembling genetic components that don’t interfere with each other.


MIT biological engineers created new genetic circuits using genes found in Salmonella (seen here) and other bacteria.
Image: NIH

Unlike electronic circuits on a silicon chip, biological circuits inside a cell cannot be physically isolated from one another. “The cell is sort of a burrito. It has everything mixed together,” says Christopher Voigt, an associate professor of biological engineering at MIT.

Because all the cellular machinery for reading genes and synthesizing proteins is jumbled together, researchers have to be careful that proteins that control one part of their synthetic circuit don’t hinder other parts of the circuit.

Voigt and his students have now developed circuit components that don’t interfere with one another, allowing them to produce the most complex synthetic circuit ever built. The circuit, described in the Oct. 7 issue of Nature, integrates four sensors for different molecules. Such circuits could be used in cells to precisely monitor their environments and respond appropriately.

“It’s incredibly complex, stitching together all these pieces,” says Voigt, who is co-director of the Synthetic Biology Center at MIT. Larger circuits would require computer programs that Voigt and his students are now developing, which should allow them to combine hundreds of circuits in new and useful ways.

Lead author of the paper is former MIT postdoc Tae Seok Moon, now an assistant professor of energy, environmental and chemical engineering at Washington University in St. Louis. Other authors are MIT postdocs Chunbo Lou and Brynne Stanton, and Alvin Tamsir, a graduate student at the University of California at San Francisco.

Expanding the possibilities

Previously, Voigt has designed bacteria that can respond to light and capture photographic images, and others that can detect low oxygen levels and high cell density — both conditions often found in tumors. However, no matter the end result, most of his projects, and those of other synthetic biologists, use a small handful of known genetic parts. “We were just repackaging the same circuits over and over again,” Voigt says.

To expand the number of possible circuits, the researchers needed components that would not interfere with each other. They started out by studying the bacterium that causes salmonella, which has a cellular pathway that controls the injection of proteins into human cells. “It’s a very tightly regulated circuit, which is what makes it a good synthetic circuit,” Voigt says.

The pathway consists of three components: an activator, a promoter and a chaperone. A promoter is a region of DNA where proteins bind to initiate transcription of a gene. An activator is one such protein. Some activators also require a chaperone protein before they can bind to DNA to initiate transcription.

The researchers found 60 different versions of this pathway in other species of bacteria, and found that most of the proteins involved in each were different enough that they did not interfere with one another. However, there was a small amount of crosstalk between a few of the circuit components, so the researchers used an approach called directed evolution to reduce it. Directed evolution is a trial-and-error process that involves mutating a gene to create thousands of similar variants, then testing them for the desired trait. The best candidates are mutated and screened again, until the optimal gene is created.

Aindrila Mukhopadhyay, a staff scientist at Lawrence Berkeley National Laboratory, says the amount of troubleshooting the researchers did to create each functional module is impressive. “A lot of people are charmed by the idea of creating complex genetic circuits. This study provides valuable examples of the types of optimizations that they may have to do in order to accomplish such goals,” says Mukhopadhyay, who was not part of the research team.

Layered circuits

To design synthetic circuits so they can be layered together, their inputs and outputs must mesh. With an electrical circuit, the inputs and outputs are always electricity. With these biological circuits, the inputs and outputs are proteins that control the next circuit (either activators or chaperones).

These components could be useful for creating circuits that can sense a variety of environmental conditions. “If a cell needs to find the right microenvironment — glucose, pH, temperature and osmolarity [solute concentration] — individually they’re not very specific, but getting all four of those things really narrows it down,” Voigt says.

The researchers are now applying this work to create a sensor that will allow yeast in an industrial fermenter to monitor their own environment and adjust their output accordingly.

The research was funded by the U.S. Office of Naval Research, the National Institutes of Health, Life Technologies, Defense Advanced Research Projects Agency and the National Science Foundation.

Sarah McDonnell | EurekAlert!
Further information:
http://www.mit.edu
http://web.mit.edu/newsoffice/2012/complex-biological-circuit-1007.html

More articles from Life Sciences:

nachricht Cnidarians remotely control bacteria
21.09.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Immune cells may heal bleeding brain after strokes
21.09.2017 | NIH/National Institute of Neurological Disorders and Stroke

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Comet or asteroid? Hubble discovers that a unique object is a binary

21.09.2017 | Physics and Astronomy

Cnidarians remotely control bacteria

21.09.2017 | Life Sciences

Monitoring the heart's mitochondria to predict cardiac arrest?

21.09.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>