The ability to program living holds tremendous potential for energy, agriculture, water remediation and medicine, and synthetic biology is on the case.
Researchers have already designed a 'tool box' of small genetic components that act as intracellular switches, logic gates, counters and oscillators but wiring those components together to form larger circuits that can function as 'genetic programs' has been difficult, because of the small number of available wires.
Okay, no more metaphors, you get the idea. A new paper describes development of a rapid and tunable post-translational coupling for genetic circuits. The advance builds on development of biopixel (square trap) sensor arrays by the same group of scientists two years ago (Nature 481, 39-44 doi:10.1038/nature10722).
Independent genetic circuits are linked within single cells, illustrated under the magnifying glass, then coupled via quorum sensing at the colony level. Credit: Arthur Prindle, UC San Diego
The problem the researchers solved arises from the noisy cellular environment that tends to lead to highly variable circuit performance. The components of a cell are intermixed, crowded and constantly bumping into each other. This makes it difficult to reuse parts in different parts of a program, limiting the total number of available parts and wires. These difficulties hindered the creation of genetic programs that can read the cellular environment and react with the execution of a sequence of instructions.
The team’s breakthrough involves another metaphor - it is like a form of “frequency multiplexing” iny FM radio.
“This circuit lets us encode multiple independent environmental inputs into a single time series,” said Arthur Prindle, a bioengineering graduate student at U.C. San Diego and the first author of the study. “Multiple pieces of information are transferred using the same part. It works by using distinct frequencies to transmit different signals on a common channel.”
The key that enabled this breakthrough is the use of frequency, rather than amplitude, to convey information. “Combining two biological signals using amplitude is difficult because measurements of amplitude involve fluorescence and are usually relative. It’s not easy to separate out the contribution of each signal,” said Prindle. “When we use frequency, these relative measurements are made with respect to time, and can be readily extracted by measuring the time between peaks using any one of several analytical methods.”
Microfluidic device containing an array of biopixels (square traps) in which bacteria grow. Credit: Arthur Prindle, UC San Diego
While their application may be inspired by electronics, they caution in their paper against what they see as increasing “metaphorization” of engineering biology. We were guilty of that in the first two paragraphs of this article, but without metaphors synthetic biology can be arcane. Colloquially people understand engineering and circuits as concepts, even if they can't build them.
“We explicitly make the point that since biology is often too intertwined to engineer in the way we are accustomed in electronics, we must deal directly with bidirectional coupling and quantitatively understand its effects using computational models,” explained Prindle. “It’s important to find the right dose of inspiration from engineering concepts while making sure you aren’t being too reliant on your engineering metaphors.”
Enabling this breakthrough is the development of an intracellular wiring mechanism that enables rapid transmission of protein signals between the individual modules. The new wiring mechanism was inspired by a previous study in the lab on the bacterial stress response. It reduces the time lags that develop as a consequence of using proteins to activate or repress genes.
“The new coupling method is capable of reducing the signaling time delay between individual genetic circuits by more than an order of magnitude,” said Jeff Hasty, a professor of biology and bioengineering at UC San Diego who headed the team of researchers and co-directs the university’s BioCircuits Institute. “The state of the art has been about 20 to 40 minutes, but we can now do it in less than one minute.”
“What’s really exciting about this coupling method is the particular way we did it,” said Prindle. “Rather than trying to build from scratch, we made use of the enzyme machinery that the cell uses for rapid and precise signaling during times of stress. This is an appealing strategy because it lets us take advantage of the advanced machinery that nature has already evolved.”
Citation: Arthur Prindle, Jangir Selimkhanov, Howard Li, Ivan Razinkov, Lev S. Tsimring, Jeff Hasty, 'Rapid and tunable post-translational coupling of genetic circuits', Nature 508, 387–391 17 April 2014 doi:10.1038/nature13238
- PHYSICAL SCIENCES
- EARTH SCIENCES
- LIFE SCIENCES
- SOCIAL SCIENCES
Subscribe to the newsletter
Stay in touch with the scientific world!
Know Science And Want To Write?
- Kudos To "The Independent" Newspaper For Debunking Nibiru "Blood Moon" Hoax
- USDA Microbiologist Warns Bacteria In Vaping Products May Be A Health Concern
- Control Cancer By Making The Tumor Cell Environment Hostile
- 20 Cent School Intervention Stops Unhealthy Weight Gain In Children
- Gödel,Frenkel, Kurzweil, and Hawkins on AI
- Your Microbiome Did Not Cause Your Weight Problem
- A Great Blitz Game
- "So, how are you doing now that you know science is real and Niribu has been confirmed and will..."
- "Im just a worried person mr walker worried that something bad is about to happen either next month..."
- "Stacey, I already have. But sometimes I find new ways to explain these things which seem to help..."
- "Mr walker please would you be able to demonstrate how this cant be real or at least show hard evidence..."
- "germs, microbes, bacteria, etc.apparently cannot feed on pg, vg, or nicotine. The flavorings commonly..."
- Breast Cancer: Genomics May Show Where Chemo Might Not Be Needed
- Gallup Poll: Great Example of How to Bias a Social Science Study
- Another Kardashian Craze Debunked
- Fad Friday: Ditch The Body Wrap!
- Commonly Cited Stat of 10 Bacteria for Every 1 Human Cell Is Wrong
- Why The EpiPen And Other Generic Drugs Are So Expensive
- Activity tracker uses heart rate to personalize amount of exercise needed to prevent death
- Moderate physical activity linked with 50 percent reduction in cardiovascular death in over-65s
- 20 cent school intervention stops unhealthy weight gain in children
- Low socioeconomic status associated with higher risk of second heart attack or stroke
- Smartphone detects atrial fibrillation with existing hardware