From Living Computers to Nano-Robots: How We’re Taking DNA Beyond Genetics

DNA is one of the most amazing molecules in nature, providing a way to carry the instructions needed to create almost any life form on Earth in a microscopic package. Now scientists are finding ways to push DNA even further, using it not just to store information but to create physical components in a range of biological machines.

Deoxyribonucleic acid or “DNA” carries the genetic information that we, and all living organisms, use to function. It typically comes in the form of the famous double-helix shape, made up of two single-stranded DNA molecules folded into a spiral. Each of these is made up of a series of four different types of molecular component: adenine (A), guanine (G), thymine (T), and cytosine (C).

Genes are made up from different sequences of these building block components, and the order in which they appear in a strand of DNA is what encodes genetic information. But by precisely designing different A, G, T and C sequences, scientists have recently been able to develop new ways of folding DNA into different origami shapes, beyond the conventional double helix.

This approach has opened up new possibilities of using DNA beyond its genetic and biological purpose, turning it into a Lego-like material for building objects that are just a few billionths of a meter in diameter (nanoscale). DNA-based materials are now being used for a variety of applications, ranging from templates for electronic nano-devices, to ways of precisely carrying drugs to diseased cells.

DNA-based nanothermometers

Designing electronic devices that are just nanometers in size opens up all sorts of possible applications but makes it harder to spot defects. As a way of dealing with this, researchers at the University of Montreal have used DNA to create ultrasensitive nanoscale thermometers that could help find minuscule hotspots in nanodevices (which would indicate a defect). They could also be used to monitor the temperature inside living cells.

The nanothermometers are made using loops of DNA that act as switches, folding or unfolding in response to temperature changes. This movement can be detected by attaching optical probes to the DNA. The researchers now want to build these nanothermometers into larger DNA devices that can work inside the human body.

Biological nanorobots

Researchers at Harvard Medical School have used DNA to design and build a nanosized robot that acts as a drug delivery vehicle to target specific cells. The nanorobot comes in the form of an open barrel made of DNA, whose two halves are connected by a hinge held shut by special DNA handles. These handles can recognize combinations of specific proteins present on the surface of cells, including ones associated with diseases.

When the robot comes into contact with the right cells, it opens the container and delivers its cargo. When applied to a mixture of healthy and cancerous human blood cells, these robots showed the ability to target and kill half of the cancer cells, while the healthy cells were left unharmed.

DNA barrel. Image credit: Campbell Strong, Shawn Douglas, and Gaël McGill.

Bio-computers in living animals

Because DNA structures can act as switches, moving from one position to another and back again, they can be used to perform the logical operations that make computer calculations possible. Researchers at Harvard and Bar-Ilan University in Israel have used this principle to build different nanoscale robots that can interact with each other, using their DNA switches to react to and produce different signals.

What’s more, the scientists implanted the robots into a living animal, in this instance a cockroach. This allowed them to develop a novel type of biological computer that can control the delivery of therapeutic molecules inside the cockroach by switching elements of their structure “on” or “off”. A trial of these DNA nanorobots is now scheduled to take place in humans.

Light-harvesting antennas

As well as creating minuscule machines, DNA can provide a way for us to copy natural processes at the nanoscale. For example, nature can capture energy from the sun using photosynthesis to convert light into chemical energy, which acts as fuel for plants and other organisms (and the animals that eat them). Researchers at Arizona State University and the University of British Columbia have now built a three-arm DNA structure that can capture and transfer light that mimics this process.

Photosynthesis occurs in living organisms thanks to tiny antennas made up of a large number of pigment molecules at specific orientations and distances from each other, which are able to absorb visible light. The artificial DNA-based structures act as similar antennas, controlling the position of specific dye molecules that absorb the light energy and channel it to a reaction centre where it is converted into chemical energy. This work could pave the way for devices capable of more efficiently using the most abundant source of energy we have at our disposal: sunlight.

So what’s next for DNA nanotechnology? It is hard to know but, with DNA, nature has given us a very versatile tool. It is now up to us to make the best use of it.

ORIGINAL: Singularity Hub

By MATTEO PALMA

ON JUN 07, 2016

Researchers Watch Tiny Living Machines Self-Assemble

ORIGINAL: Science Daily

Vallée-Bélisle and Michnick have developed a new approach to visualize how proteins assemble, which may also significantly aid our understanding of diseases such as Alzheimer’s and Parkinson’s, which are caused by errors in assembly. Here shown are two different assembly stages (purple and red) of the protein ubiquitin and the fluorescent probe used to visualize these stage (tryptophan: see yellow). (Credit: Peter Allen)

ScienceDaily (June 10, 2012) — Enabling bioengineers to design new molecular machines for nanotechnology applications is one of the possible outcomes of a study by University of Montreal researchers that was published in Nature Structural and Molecular Biology June 10. The scientists have developed a new approach to visualize how proteins assemble, which may also significantly aid our understanding of diseases such as Alzheimer's and Parkinson's, which are caused by errors in assembly. 

"In order to survive, all creatures, from bacteria to humans, monitor and transform their environments using small protein nanomachines made of thousands of atoms," explained the senior author of the study, Prof. Stephen Michnick of the university's department of biochemistry. "For example, in our sinuses, there are complex receptor proteins that are activated in the presence of different odor molecules. Some of those scents warn us of danger; others tell us that food is nearby." Proteins are made of long linear chains of amino acids, which have evolved over millions of years to self-assemble extremely rapidly - often within thousandths of a split second -- into a working nanomachine. "One of the main challenges for biochemists is to understand how these linear chains assemble into their correct structure given an astronomically large number of other possible forms," Michnick said.

"To understand how a protein goes from a linear chain to a unique assembled structure, we need to capture snapshots of its shape at each stage of assembly" said Dr. Alexis Vallée-Bélisle, first author of the study. "The problem is that each step exists for a fleetingly short time and no available technique enables us to obtain precise structural information on these states within such a small time frame. We developed a strategy to monitor protein assembly by integrating fluorescent probes throughout the linear protein chain so that we could detect the structure of each stage of protein assembly, step by step to its final structure."

The protein assembly process is not the end of its journey, as a protein can change, through chemical modifications or with age, to take on different forms and functions. "Understanding how a protein goes from being one thing to becoming another is the first step towards understanding and designing protein nanomachines for biotechnologies such as medical and environmental diagnostic sensors, drug synthesis of delivery," Vallée-Bélisle said.

This research was supported by the Natural Sciences and Engineering Research Council of Canada and Le fond de recherché du Québec, Nature et Technologie. The article, "Visualizing transient protein folding intermediates by tryptophan scanning mutagenesis," published in Nature Structural & Molecular Biology, was coauthored by Alexis Vallée-Bélisle and Stephen W. Michnick of the Département de Biochimie de l'Université de Montréal. The University of Montreal is known officially as Université de Montréal.