Glowing, Blinking Bacteria Reveal How Cells Synchronize Biological Clocks

Glowing, Blinking Bacteria Reveal How Cells Synchronize Biological Clocks

  5:17:00 PM    Science Lover

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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.

Green fluorescent protein causes the E. coli to glow 
when the cells' clock is activated. (Credit: UC San Diego)

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."

To study the process of entrainment at the genetic level, Hasty and his team of researchers at UC San Diego's Biocircuits Institute combined techniques from synthetic biology, microfluidic technology and computational modeling to build a microfluidic chip with a series of chambers containing populations of E. coli bacteria. Within each bacterium, the genetic machinery responsible for the biological clock oscillations was tied to green fluorescent protein, which caused the bacteria to periodically fluoresce.



To simulate day and night cycles, the researchers modified the bacteria to glow and blink whenever arabinose -- a chemical that triggered the oscillatory clock mechanisms of the bacteria -- was flushed through the microfluidic chip. In this way, the scientists were able to simulate periodic day-night cycles over a period of only minutes instead of days to better understand how a population of cells synchronizes its biological clocks.

Hasty said a similar microfluidic system in principal could be constructed with mammalian cells to study how human cells synchronize with light and darkness. Such genetic model systems would have important future applications since scientists have discovered that problems with the biological clock can result in many common medical problems from diabetes to sleep disorders.

Other members of Hasty's team included Lev Tsimring, associate director of the BioCircuits Institute, and bioengineering graduate students Octavio Mondragon, Tal Danino and Jangir Selimkhanov. Their research was supported by grants from the National Institutes of Health and General Medicine and the San Diego Center for Systems Biology.

Story Source: The above story is reprinted (with editorial adaptations) from materials provided by University of California - San Diego.

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Nano-engineered cotton promises to wipe out water bugs

Nano-engineered cotton promises to wipe out water bugs

  2:02:00 AM    Science Lover

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COTTON impregnated with silver nanowires and carbon nanotubes (CNTs) could provide a cheap and effective method of purifying water in remote locations.

A new filter needs only gravity and a weak electric current to produce its sterilising effect, making it suitable for a portable water-treatment device.

The fabric is easy to produce, says lead researcher Yi Cui at Stanford University in California. Cui's team simply dip a piece of cotton into a solution of CNTs and then pipette droplets containing silver nanowires onto the cotton.

Prepare to die, E. coli (Image: Linda Stannard/UCT/SPL)

Analysing the fabric with a scanning electron microscope reveals that the CNTs stick to the individual cotton fibres, while the slightly larger silver nanowires form a mesh between the fibres. The nanoparticles enable the fabric to conduct electricity, so a weak electric current can run across it. This helps kill bacteria by damaging their outer membranes, while the silver nanowires' anti-bacterial properties do the rest.

So when Cui and his colleagues poured water contaminated with the bacterium Escherichia coli (pictured) through the silver-coated, electrically-conducting fabric, they found it killed 89 per cent of the bacteria. By conducting three successive runs through the fabric, they were able to kill over 98 per cent - enough to make the water safe to drink (Nano Letters, DOI: 10.1021/nl101944e).

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Medical Micro-robots Made As Small As Bacteria

Medical Micro-robots Made As Small As Bacteria

  8:57:00 PM    Science Lover

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Artificial bacterial flagella are about half as long as the thickness of a human hair.
They can swim at a speed of up to one body length per second.
This means that they already resemble their natural role models very closely.
(Credit: Institute of Robotics and Intelligent Systems/ETH Zurich)

For the first time, ETH Zurich researchers have built micro-robots as small as bacteria. Their purpose is to help cure human beings.

They look like spirals with tiny heads, and screw through the liquid like miniature corkscrews. When moving, they resemble rather ungainly bacteria with long whip-like tails. They can only be observed under a microscope because, at a total length of 25 to 60 µm, they are almost as small as natural flagellated bacteria. Most are between 5 and 15 µm long, a few are more than 20 µm.

Mimicking nature

The tiny spiral-shaped, nature-mimicking lookalikes of E. coli and similar bacteria. are called “Artificial Bacterial Flagella” (ABFs), the “flagella” referring to their whip-like tails. They were invented, manufactured and enabled to swim in a controllable way by researchers in the group led by Bradley Nelson, Professor at the Institute of Robotics and Intelligent Systems at ETH Zurich. In contrast to their natural role model, some of which cause diseases, the ABFs are intended to help cure diseases in the future.

The practical realization of these artificial bacteria, the smallest yet created, with a rigid flagellum and external actuation, was made possible mainly by the self-scrolling technique from which the spiral-shaped ABFs are constructed. ABFs are fabricated by vapor-depositing several ultra-thin layers of the elements indium, gallium, arsenic and chromium onto a substrate in a particular sequence. They are then patterned from it by means of lithography and etching. This forms super-thin, very long narrow ribbons that curl themselves into a spiral shape as soon as they are detached from the substrate, because of the unequal molecular lattice structures of the various layers. Depending on the deposited layer thickness and composition, a spiral is formed with different sizes which can be precisely defined by the researchers. Nelson says, “We can specify not only how small the spiral is, but even the scrolling direction of the ribbon that forms the spiral.”

External propulsion via magnetic field

Even before releasing the ribbon that will afterwards form the artificial flagellum, a kind of head for the mini-robot is attached to one of its ends. It consists of a chromium-nickel-gold tri-layer film, also vapor-deposited. Nickel is soft-magnetic, in contrast to the other materials used, which are non-magnetic. Nelson explains that, “This tiny magnetic head enables the ABF to move in a specific way in a magnetic field.” The spiral-shaped ABF swim through the liquid and its movements can be observed and recorded under a microscope.

With the software developed by the group, the ABF can be steered to a specific target by tuning the strength and direction of the rotating magnetic field which is generated by several coils. The ABFs can move forwards and backwards, upwards and downwards, and can also rotate in all directions. Brad Nelson says “There’s a lot of physics and mathematics behind the software.” The ABFs do not need energy of their own to swim, nor do they have any moving parts. The only decisive thing is the magnetic field, towards which the tiny head constantly tries to orientate itself and in whose direction it moves. The ABFs currently swim at a speed of up to 20 µm, i.e. up to one body length, per second. Nelson expects that it will be possible to increase the speed to more than 100 µm per second. For comparison: E. coli swims at 30 µm per second.

Possible applications in medicine

The ABFs have been designed for biomedical applications. For example, they could carry medicines to predetermined targets in the body, remove plaque deposits in the arteries or help biologists to modify cellular structures that are too small for direct manipulation by researchers. In initial experiments, the ETH Zurich researchers have already made the ABFs carry around polystyrene micro-spheres.

At the moment, however, the group is still carrying out basic research. Further investigations will be needed before there can be any practical applications. Nelson explains that, “For applications in the human body, it would first of all be necessary to steer the ABFs precisely, track their route without optical monitoring and guarantee their localization at all times.” If ABFs are to deliver drugs, they would first of all have to be functionalized in a feasible way and then need to be able to release the drugs precisely in situ. The plan is for the ABFs themselves to become even faster and smaller. Nelson is enthusiastic about how ingeniously nature has designed natural bacteria. He is happy that his group’s ABFs already resemble the originals so closely.

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