Engineered Bacteria Store Memories of Chemical Exposure

New research from MIT reveals that engineered E. coli can store long-term memories of chemical exposure and other events in their DNA.

MIT engineers have transformed the genome of the bacterium E. coli into a long-term storage device for memory. They envision that this stable, erasable, and easy-to-retrieve memory will be well suited for applications such as sensors for environmental and medical monitoring.

“You can store very long-term information,” says Timothy Lu, an associate professor of electrical engineering and computer science and biological engineering. “You could imagine having this system in a bacterium that lives in your gut, or environmental bacteria. You could put this out for days or months, and then come back later and see what happened at a quantitative level.”

The new strategy, described in the journal Science, overcomes several limitations of existing methods for storing memory in bacterial genomes, says Lu, the paper’s senior author. Those methods require a large number of genetic regulatory elements, limiting the amount of information that can be stored.

The earlier efforts are also limited to digital memory, meaning that they can record only all-or-nothing memories, such as whether a particular event occurred. Lu and graduate student Fahim Farzadfard, the paper’s lead author, set out to create a system for storing analog memory, which can reveal how much exposure there was, or how long it lasted. To achieve that, they designed a “genomic tape recorder” that lets researchers write new information into any bacterial DNA sequence.

Stable memory

To program E. coli bacteria to store memory, the MIT researchers engineered the cells to produce a recombinase enzyme, which can insert DNA, or a specific sequence of single-stranded DNA, into a targeted site. However, this DNA is produced only when activated by the presence of a predetermined molecule or another type of input, such as light.

After the DNA is produced, the recombinase inserts the DNA into the cell’s genome at a preprogrammed site. “We can target it anywhere in the genome, which is why we’re viewing it as a tape recorder, because you can direct where that signal is written,” Lu says.

Once an exposure is recorded through this process, the memory is stored for the lifetime of the bacterial population and is passed on from generation to generation.

There are a couple of different ways to retrieve this stored information. If the DNA is inserted into a nonfunctional part of the genome, sequencing the genome will reveal whether the memory is stored in a particular cell. Or, researchers can target the sequences to alter a gene. For example, in this study, the new DNA sequence turned on an antibiotic resistance gene, allowing the researchers to determine how many cells had gotten the memory sequence by adding antibiotics to the cells and observing how many survived.

By measuring the proportion of cells in the population that have the new DNA sequence, researchers can determine how much exposure there was and how long it lasted. In this paper, the researchers used the system to detect light, a lactose metabolite called IPTG, and an antibiotic derivative called aTc, but it could be tailored to many other molecules or even signals produced by the cell, Lu says.

The information can also be erased by stimulating the cells to incorporate a different piece of DNA in the same spot. This process is currently not very efficient, but the researchers are working to improve it.

“This work is very exciting because it integrates many useful capabilities in a single system: long-lasting, analog, distributed genomic storage with a variety of readout options,” says Shawn Douglas, an assistant professor at the University of California at San Diego who was not involved in the study. “Rather than treating each individual cell as a digital storage device, Farzadfard and Lu treat an entire population of cells as an analog ‘hard drive,’ greatly increasing the total amount of information that can be stored and retrieved.”

Bacterial sensors

Environmental applications for this type of sensor include monitoring the ocean for carbon dioxide levels, acidity, or pollutants. In addition, the bacteria could potentially be designed to live in the human digestive tract to monitor someone’s dietary intake, such as how much sugar or fat is being consumed, or to detect inflammation from irritable bowel disease.

These engineered bacteria could also be used as biological computers, Lu says, adding that they would be particularly useful in types of computation that require a lot of parallel processing, such as picking patterns out of an image.

“Because there are billions and billions of bacteria in a given test tube, and now we can start leveraging more of that population for memory storage and for computing, it might be interesting to do highly parallelized computing. It might be slow, but it could also be energy-efficient,” he says.

Another possible application is engineering brain cells of living animals or human cells grown in a petri dish to allow researchers to track whether a certain disease marker is expressed or whether a neuron is active at a certain time. “If you could turn the DNA inside a cell into a little memory device on its own and then link that to something you care about, you can write that information and then later extract it,” Lu says.

The research was funded by the National Institutes of Health, the Office of Naval Research, and the Defense Advanced Research Projects Agency.

Publication: Fahim Farzadfard and Timothy K. Lu, “Genomically encoded analog memory with precise in vivo DNA writing in living cell populations,” Science 14 November 2014: Vol. 346 no. 6211; DOI: 10.1126/science.1256272

Source: Anne Trafton, MIT News

New Theory Suggests Quantum Effects Caused by Interacting Parallel Worlds

A new theory of quantum mechanics presumes not only that parallel worlds exist, but also that their mutual interaction is what gives rise to all quantum effects observed in nature.

The theory, first published by Professor Bill Poirier four years ago, has recently attracted attention from the foundational physics community, leading to an invited Commentary in a top-ranking physics journal, Physical Review X.

According to Poirier’s theory, quantum reality is not wave-like at all, but is comprised of multiple, classical-like worlds. In each of these worlds, every object has very definite physical attributes, such as position and momentum. Within a given world, objects interact with each other classically. All quantum effects, on the other hand, manifest as interactions between “nearby” parallel worlds.

The idea of many worlds is not new. In 1957, Hugh Everett III published what is now called the “Many Worlds” interpretation of quantum mechanics. “But in Everett’s theory, the worlds are not well defined,” according to Poirier, “because the underlying mathematics is that of the standard wave-based quantum theory.”

In contrast, in Poirier’s “Many Interacting Worlds” theory, the worlds are built into the mathematics right from the start.

Does this prove anything definitive about the nature of reality? “Not yet,” says Poirier. “Experimental observations are the ultimate test of any theory. So far, Many Interacting Worlds makes the same predictions as standard quantum theory, so all we can say for sure at present is that it might be correct.”

Poirier first arrived at the idea unexpectedly, in the pursuit of a much more practical goal. “I didn’t just sit down one day and say ‘gosh, let’s invent a crazy new quantum interpretation with interacting parallel worlds.’ I was trying to develop an efficient computational method using something called quantum trajectories, when it suddenly hit me how you could get everything from the trajectories (i.e. the worlds) themselves, without actually needing any wave.”

Poirier published both the new mathematics and the new interpretation in a 2010 Chemical Physics paper, leading to a collaboration with mathematician Jeremy Schiff at Bar-Ilan University. This in turn led to a 2012 publication in the Journal of Chemical Physics which—with over 20,000 downloads—is one of the most downloaded papers in that journal’s history. More recently, this work has garnered the attention of the broader community. “We are very pleased that other physicists and even philosophers are now getting involved,” says Poirier.

One such researcher is Australian physicist Howard Wiseman of Griffith University in Brisbane. “I am very glad to have met Bill,” says Wiseman, adding that Poirier is “taking literally this idea that you have an ensemble of particles…rather than just an individual one.” Wiseman and coworkers recently submitted their first article on Many Interacting Worlds to Physical Review X, which was published together with Poirier’s Commentary. Wiseman’s approach is a discrete version, for which “there is a finite but extremely large ensemble of particles…well, ensemble of worlds, I should say,” he explains.

Regarding the mathematical developments in Wiseman’s article, Poirier says, “These are great ideas—not only conceptually, but also with regard to the new numerical breakthroughs they are almost certain to engender. Our group offered the foundational physics community a new interpretation of quantum mechanics; in effect, they have now returned the favor, by offering us a promising new computational method.”

Bill Poirier is Chancellor’s Council Distinguished Research Professor and also Barnie E. Rushing Jr. Distinguished Faculty Member at Texas Tech University, in the Department of Chemistry and Biochemistry and also the Department of Physics.

Publications:

1. Michael J. W. Hall, et al., “Quantum Phenomena Modeled by Interactions between Many Classical Worlds,” Physical Review X, 2014; 4 (4);doi:10.1103/PhysRevX.4.041013
2. Bill Poirier, “Does Research on Foundations of Quantum Mechanics Fit into PRX’s Scope?,” Physical Review X, 2014; doi:10.1103/PhysRevX.4.040002
3. Jeremy Schiff and Bill Poirier, “Communication: Quantum mechanics without wavefunctions,” The Journal of Chemical Physics, 2012; 136 (3): 031102;doi:10.1063/1.3680558
4. Bill Poirier,” Bohmian mechanics without pilot waves,” Chemical Physics, 2010; 370 (1-3) 4; doi:10.1016/j.chemphys.2009.12.024

Source: Texas Tech University

Scientists Develop a Nanolamp with a Lightning-Fast Switch

Researchers at the Max Planck Institute for Solid State Research apply a voltage between a gold surface coated with a layer of spherical carbon molecules and the tip of a scanning tunneling microscope. The resulting electric field (indicated by the grey arrows in the diagram) can be regulated by the level of the voltage and the distance between the tip and the metal surface. With a particular field strength, the single molecule (in magenta) becomes electrically charged, which immediately leads to electrical energy being converted to light (the yellow wave). Credit: MPI for Solid State Research

Scientists have developed a light source which converts an electrical voltage pulse into a light pulse by means of a single molecule, possibly serving as a prototype for nano-components that convert electrical into optical signals with gigahertz frequencies.

Information is processed and transmitted by ever-smaller components, sometimes with electrons and sometimes with light. Scientists at the Max Planck Institute for Solid State Research in Stuttgart have now developed a light source which converts an electrical voltage pulse into a light pulse by means of a single molecule. Here the molecule functions as a transistor-controlled light switch which even allows the intensity of the light to be regulated. Since the molecular switch allows the light to be switched on and off extremely fast, the light source could serve as a prototype for nano-components that convert electrical into optical signals with gigahertz frequencies.

Today, organic dyes do not just provide color for carpets, newspapers or clothing when light shines on them. Now they themselves shine in electric light sources, in organic light-emitting diodes (OLEDs), like those in smartphone screens. However, the displays still contain transistors for regulating the brightness alongside the actual light sources (pixels). A team from the Max Planck Institute for Solid State Research, the Max Planck EPFL Center and the Karlsruhe Institute of Technology, has now combined the two functions in a single molecule.

The researchers working with Klaus Kern, Director of the Stuttgart-based Max Planck Institute, construct their nanolamp with integrated transistor control by placing a dye molecule on a layer of Buckminsterfullerenes – which are spherical carbon molecules. The layer of carbon spheres coats a metal carrier, in this case of gold, which serves as an electrode. “As the second electrode above the dye molecule, we use the tip of a scanning tunneling microscope,” says Klaus Kuhnke. “But a second metal layer would also be suitable.” However, the researchers were only able to discover the astonishing properties of the individual molecule because they used a movable tip for their investigation. What they actually did was to scan the surface with the tip, measuring the light emitted at the same time. “In the process we observed that light is produced on the dye molecules,” according to Kuhnke.

The voltage first produces light waves which are trapped on the metal surface

The researchers now regulate the electric field on the molecule with an electrical voltage between the gold carrier and the tip of the scanning tunneling microscope (STM), as well as the distance between the two electrical contacts. If this exceeds 2.5 volts per nanometer, the lamp is switched on. The molecule, however, does not just switch the light on and off. It actually allows continuous regulation of the light intensity, getting brighter and darker over a very narrow band of a few millivolts. It thus functions in this range similarly to a light-emitting transistor.

The electrical energy is not converted directly into light energy in the switching process, but indirectly via “plasmons”. These can be imagined as light waves that are trapped on the metallic surface and may be radiated by such things as surface irregularities. With their help, more information can be transmitted or processed in a small space in the form of light than with light alone: plasmons can run along metal tracks which are narrower than 100 nanometers, whereas optical fibers, for instance, must be at least half as wide as the wavelength of the light they transmit.

The switching process takes less than a billionth of a second

The organic molecule plays a decisive role in the generation of the trapped and radiated light waves on the metal surface: a minimal change in the electric field at the location of the molecule decides whether light is produced or not. This makes the nanolamp interesting for the transfer of digital information with light, where “light on” stands for the one of a data bit and “light off” for the zero. “A small modulation of the electric field at the molecule produces a bit stream that is emitted as light and can transfer a message,” says Klaus Kuhnke. And since a light source above the threshold value turns on with a tiny change in voltage, the switching process takes place extremely quickly: It takes less than a billionth of a second, and so may eventually permit data transfers with bit rates in the gigahertz range.

The control of the intensity of the light by a single molecule is decisive for the speed of the light switch. Mechanical light switches are operated by a lever, and the heavier this lever is the more effort it takes to move the switch from one switching position to another. These clumsy levers correspond in electronics to unavoidable capacitances which swallow a part of the current without producing any light. The larger the light-switching element is, the more time and energy is required to charge the “parasitic” capacitors. Here the minute size of the molecule helps: It costs hardly any additional energy to charge the environment of a single molecule the size of a millionth of a millimeter with a tiny voltage of a few millivolts – the switching process is correspondingly fast. “Such a molecular light source thus promises to become a new, efficient component for information transmission – especially as the light produced may still be weak, but is clearly perceptible with the naked eye,” says Klaus Kuhnke.

Publication: Christoph Große, et al., “Dynamic Control of Plasmon Generation by an Individual Quantum System,” Nano Letters, 2014, 14 (10), pp 5693–5697; DOI: 10.1021/nl502413k