Wednesday, September 18, 2019

DNA 'origami' takes flight in emerging field of nano machines

Making things out of DNA, nicknamed DNA origami after the traditional Japanese paper craft, is moving from a nanoscale novelty to a practical research tool. Emory chemists Khalid Salaita and Aaron Blanchard wrote about the emerging field of DNA mechanotechnology for the journal Science. (Getty Images)

By Carol Clark

Just as the steam engine set the stage for the Industrial Revolution, and micro transistors sparked the digital age, nanoscale devices made from DNA are opening up a new era in bio-medical research and materials science.

The journal Science describes the emerging uses of DNA mechanical devices in a “Perspective” article by Khalid Salaita, a professor of chemistry at Emory University, and Aaron Blanchard, a graduate student in the Wallace H. Coulter Department of Biomedical Engineering, a joint program of Georgia Institute of Technology and Emory.

The article heralds a new field, which Blanchard dubbed “DNA mechanotechnology,” to engineer DNA machines that generate, transmit and sense mechanical forces at the nanoscale.

“For a long time,” Salaita says, “scientists have been good at making micro devices, hundreds of times smaller than the width of a human hair. It’s been more challenging to make functional nano devices, thousands of times smaller than that. But using DNA as the component parts is making it possible to build extremely elaborate nano devices because the DNA parts self-assemble.”

Aaron Blanchard, left, an Emory graduate student of chemistry, and Khalid Salaita, professor of chemistry, are working at the forefront of DNA mechanotechnology.

DNA, or deoxyribonucleic acid, stores and transmits genetic information as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C) and thymine (T). The DNA bases have a natural affinity to pair up with each other — A with T and C with G. Synthetic strands of DNA can be combined with natural DNA strands from bacteriophages. By moving around the sequence of letters on the strands, researchers can get the DNA strands to bind together in ways that create different shapes. The stiffness of DNA strands can also easily be adjusted, so they remain straight as a piece of dry spaghetti or bend and coil like boiled spaghetti.

The idea of using DNA as a construction material goes back to the 1980s, when biochemist Nadrian Seeman pioneered DNA nanotechnology. This field uses strands of DNA to make functional devices at the nanoscale. The ability to make these precise, three-dimensional structures began as a novelty, nicknamed DNA origami, resulting in objects such as a microscopic map of the world and, more recently, the tiniest-ever game of tic-tac-toe, played on a DNA board.

Work on novelty objects continues to provide new insights into the mechanical properties of DNA. These insights are driving the ability to make DNA machines that generate, transmit and sense mechanical forces.

“If you put together these three main components of mechanical devices, you begin to get hammers and cogs and wheels and you can start building nano machines,” Salaita says. “DNA mechanotechnology expands the opportunities for research involving biomedicine and materials science. It’s like discovering a new continent and opening up fresh territory to explore.”

Watch a video about how DNA machines work


Potential uses for such devices include drug delivery devices in the form of nano capsules that open up when they reach a target site, nano computers and nano robots working on nanoscale assembly lines.

The use of DNA self-assembly by the genomics industry, for biomedical research and diagnostics, is further propelling DNA mechanotechnology, making DNA synthesis inexpensive and readily available. “Potentially anyone can dream up a nano-machine design and make it a reality,” Salaita says.

He gives the example of creating a pair of nano scissors. “You know that you need two rigid rods and that they need to be linked by a pivot mechanism,” he says. “By tinkering with some open-source software, you can create this design and then go onto a computer and place an order to custom synthesize your design. You’ll receive your order in a tube. You simply put the tube contents into a solution, let your device self-assemble, and then use a microscope to see if it works the way you thought that it would.”

The Salaita Lab is one of only about 100 around the world working at the forefront of DNA mechanotechnology. He and Blanchard developed the world’s strongest synthetic DNA-based motor, which was recently reported in Nano Letters.

A key focus of Salaita’s research is mapping and measuring how cells push and pull to learn more about the mechanical forces involved in the human immune system. Salaita developed the first DNA force gauges for cells, providing the first detailed view of the mechanical forces that one molecule applies to another molecule across the entire surface of a living cell. Mapping such forces may help to diagnose and treat diseases related to cellular mechanics. Cancer cells, for instance, move differently from normal cells, and it is unclear whether that difference is a cause or an effect of the disease.

Watch a video about the Salaita Lab's work with T cells


In 2016, Salaita used these DNA force gauges to provide the first direct evidence for the mechanical forces of T cells, the security guards of the immune system. His lab showed how T cells use a kind of mechanical “handshake” or tug to test whether a cell they encounter is a friend or foe. These mechanical tugs are central to a T cell’s decision for whether to mount an immune response.

“Your blood contains millions of different types of T cells, and each T cell is evolved to detect a certain pathogen or foreign agent,” Salaita explains. “T cells are constantly sampling cells throughout your body using these mechanical tugs. They bind and pull on proteins on a cell’s surface and, if the bond is strong, that’s a signal that the T cell has found a foreign agent.”

Salaita’s lab built on this discovery in a paper recently published in the Proceedings of the National Academy of Sciences (PNAS). Work led by Emory chemistry graduate student Rong Ma refined the sensitivity of the DNA force gauges. Not only can they detect these mechanical tugs at a force so slight that it is nearly one-billionth the weight of a paperclip, they can also capture evidence of tugs as brief as the blink of an eye.

The research provides an unprecedented look at the mechanical forces involved in the immune system. “We showed that, in addition to being evolved to detect certain foreign agents, T cells will also apply very brief mechanical tugs to foreign agents that are a near match,” Salaita says. “The frequency and duration of the tug depends on how closely the foreign agent is matched to the T cell receptor.”

The result provides a tool to predict how strong of an immune response a T cell will mount. “We hope this tool may eventually be used to fine tune immunotherapies for individual cancer patients,” Salaita says. “It could potentially help engineer T cells to go after particular cancer cells.”

Related:
Nano-walkers take speedy leap forward with first rolling DNA-based motor
T cells use 'handshakes' to sort friends from foes 
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Chemists reveal the force within you

Wednesday, September 11, 2019

Chameleons inspire 'smart skin' that changes color in the sun


A chameleon can alter the color of its skin so it either blends into the background to hide or stands out to defend its territory and attract a mate. The chameleon makes this trick look easy, using photonic crystals in its skin. Scientists, however, have struggled to make a photonic crystal “smart skin” that changes color in response to the environment, without also changing in size.

The journal ACS Nano published research led by chemists at Emory University that found a solution to the problem. They developed a flexible smart skin that reacts to heat and sunlight while maintaining a near constant volume.

“Watching a chameleon change colors gave me the idea for the breakthrough,” says first author Yixiao Dong, a PhD candidate in Emory’s Department of Chemistry. “We’ve developed a new concept for a color-changing smart skin, based on observations of how nature does it.”

Read the whole story and watch videos of the color-changing process here.

Getty Images

Tuesday, August 20, 2019

Skeletal shapes key to rapid recognition of objects

"You can think of it like a child's stick drawing of a person," says Emory psychologist Stella Lourenco, explaining the skeletal geometry that aids the vision system in object recognition. (Getty Images)

By Carol Clark

In the blink of an eye, the human visual system can process an object, determining whether it’s a cup or a sock within milliseconds, and with seemingly little effort. It’s well-established that an object’s shape is a critical visual cue to help the eyes and brain perform this trick. A new study, however, finds that while the outer shape of an object is important for rapid recognition, the object’s inner “skeleton” may play an even more important role.

Scientific Reports published the research by psychologists at Emory University, showing that a key visual tool for object recognition is the medial axis of an object, or its skeletal geometry.

“When we think of an object’s shape, we typically imagine the outer contours,” explains Vladislav Ayzenberg, first author of the paper and an Emory PhD candidate in psychology. “But there is also a deeper, more abstract property of shape that’s described by skeletal geometry. Our research suggests that this inner, invisible mechanism may be crucial to recognizing an object so quickly.”

“You can think of it like a child’s stick drawing of a person,” adds Stella Lourenco, senior author of the study and an associate professor of psychology at Emory. “Using a stick figure to represent a person gives you the basic visual information you need to immediately perceive the figure’s meaning.”

The Lourenco lab researches human visual perception, cognition and development. Visual perception of an object begins when light hits our eyes and the object is projected as a two-dimensional image onto the photoreceptor cells of the retina.

“A lot of internal machinery is whirring between the eyes and brain to facilitate perception and recognition within 70 milliseconds,” Ayzenberg says. “I’m fascinated by the neural computations that go into that process.”

Although most people take it for granted, object recognition is a remarkable feat. “You can teach a two-year-old what a dog is by pointing out a real dog or showing the child a picture in a book,” Lourenco says. “After seeing such examples a child can rapidly and with ease recognize other dogs as dogs, despite variations in their individual appearances.”



The human ability at object recognition is robust despite changes in a class of objects such as outer contours, sizes, textures and colors. For the current paper, the researchers developed a series of experiments to test the role of skeletal geometry in the process.

In one experiment, participants were presented with paired images of 150 abstract 3D objects on a computer. The objects had 30 different skeletal structures. Each object was rendered with five different surface forms, to change the visible shape of the object, without altering the underlying skeleton. The participants were asked to judge whether each pair of images showed the same or different objects. The results found that skeletal similarity was a significant predictor for a correct response.

A second experiment, based on adaptations of three of the objects, tested the effects of proportional changes to the shape skeleton. Participants were able to accurately predict object similarity at a rate significantly above chance at every level of skeletal change.

A third experiment tested whether an object’s skeleton was a better predictor of object similarity than its surface form. Participants successfully matched objects by their skeletal structure or surface forms when each cue was presented in isolation. They showed a preference, however, to match objects by their skeletons, as opposed to their surface forms, when these cues conflicted with one another.

The results suggest that the visual system is not only highly sensitive to the skeletal structure of objects, but that this sensitivity may play an even bigger role in shape perception than object contours.

“Skeletal geometry appears to be more important than previously realized, but it is certainly not the only tool used in object recognition,” Lourenco says. “It may be that the visual system starts with the skeletal structure, instead of the outline of an object, and then maps other properties, such as textures and colors, onto it.”

In addition to adding to fundamental knowledge of the human vision system, the study may give insights into improving capabilities for artificial intelligence (AI). Rapid and accurate object recognition, for example, is vital for AI systems on self-driving cars.

“The best model for a machine-learning system is likely a human-learning system,” Ayzenberg says. “The human vision system has solved the problem of object recognition through evolution and adapted quite well.”

Related:
Babies' spatial reasoning predicts later math skills
How babies use numbers, space and time 
How fear skews our spatial perception
Psychologists closing in on claustrophobia 

Thursday, August 1, 2019

Protection from mosquitoes key to avoid West Nile virus

"In Georgia, West Nile virus is primarily spread by the southern house mosquito Culex quinquefasciatus," says Gonzalo Vazquez-Prokopec, associate professor in Emory's Department of Environmental Sciences. (CDC/James Gathany)

August to September is the peak of the West Nile virus (WNV) season and Atlanta area health officials have reported finding mosquitoes testing positive for the pathogen, including from 11 locations across DeKalb County. No human cases, however, have been reported.

WNV is most commonly spread to people by the bite of an infected mosquito. Most people who become infected do not feel sick, but about one in five develop a fever and other symptoms. And about one out of 150 people infected develop a serious, sometimes fatal, illness, according to the CDC.

Gonzalo Vazquez-Prokopec, associate professor in Emory University's Department of Environmental Sciences, is an expert in mosquito-borne diseases. His lab has studied the urban ecology of metro Atlanta and the Culex mosquito — a vector for WNV and other human pathogens.

Vazquez-Prokopec is currently in the field in Brazil, but we caught up with him via email for a brief Q and A.

What should people know about the particular type of mosquito that spreads WNV?

In Georgia, West Nile virus is primarily spread by the southern house mosquito Culex quinquefasciatus. This light-brown colored species bites at dusk and dawn, and is found in high numbers in and around houses and in open areas, such as parks.

Is it normal to detect WNV in so many Atlanta-area mosquitoes this time of year? 

Yes, the infection rates in mosquitoes, gathered from different mosquito traps, are following trends that we’ve seen in previous years. What we do not see is human cases — so far this year none have been reported for Georgia.

Is Atlanta normally at higher or average risk for human cases of WNV? 

Human infection with WNV is low in Georgia compared to some states in the Northeast or Midwest. This is remarkably different from what we see in mosquitoes and birds which, in Atlanta, have equally high WNV levels compared to the Northeast and Midwest. What seems to be different is the rate of spillover of the virus, or transfer from the wildlife cycle to humans, which definitely appears to be suppressed in the Southeastern United States.

How can people best protect themselves? 

Reducing human exposure to Culex mosquitoes is key to maintaining the low rates of human infection. It’s best to follow the recommendations on the CDC web site to use insect repellent and wear long-sleeved shirts and long pants when outside to protect yourself from mosquito bites, and to remove any standing water around your home. Dekalb County has a great checklist on its web site to help locate potential mosquito breeding sites around your yard.

Related:
Cardinals may reduce West Nile virus spillover in Atlanta
Sewage raises West Nile virus risk

Wednesday, July 31, 2019

Chemists teach old drug new tricks to target deadly staph bacteria

Emory chemist Bill Wuest, far right, with some of his graduate students, from left: Erika Csatary, Madeleine Dekarske and Ingrid Wilt. Photo by Ann Watson.

"Saying superbugs, one antibiotic at a time,” is the motto of Bill Wuest’s chemistry lab at Emory University. Wuest (it rhymes with “beast”) leads a team of students fighting drug-resistant bacteria — some of the scariest, most dangerous bugs on the planet.

Most recently, they created new molecules for a study published in PNAS. Their work helped verify how bithionol — a drug used to treat parasitic infections — can weaken the cell membranes of “persister” cells of methicillin-resistant Staphylococcus aureus (MRSA), a deadly staph bacterium. They also synthesized new compounds, to learn more about how bithionol works and enhance its potential for clinical use.

“Just before I entered graduate school, my mother was diagnosed with a severe staph infection,” says Ingrid Wilt, a PhD candidate, explaining what drives her passion to tackle MRSA.

“She was in a hospital in the ICU for about two weeks,” Wilt adds. “Luckily, a last-resort antibiotic worked for her and she’s okay now.”

Click here to read the full story.

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