Duke Research Blog

Following the people and events that make up the research community at Duke.

Author: Kara Manke (Page 1 of 4)

Not Your Basic Bench: Zebrafish Reveal Secrets of the Developing Gut

Our intestine is a highly complex organ – a tortuous, rugged channel built of many specialized cell-types and coated with a protective, slimy matrix. Yet the intestine begins as a simple tube consisting of a central lumen lined by a sheet of epithelial cells, which are smooth cells that lie on the surface of the lumen. These intestinal epithelial cells are central players in many human diseases.

A portrait of Daniel Levic

Daniel Levic, a postdoctoral research associate in the department of cell biology at the Duke University Medical Center.

Daniel Levic of the Bagnat Lab is using zebrafish as experimental models to understand how intestines are formed in hopes of finding new ways to combat disease. He wants to learn how the intestinal lumen forms during early development, and how intestinal epithelial cells take on their physiological functions.

Levic, a postdoctoral research associate in the department of cell biology at the Duke University Medical Center, focuses on projects in both basic and translational science. Daniel uses zebrafish to analyze the formation of the lumen and the polarity of epithelial cells — how specialized they are for carrying out different functions —  at the genetic and cellular level. He focuses on how membrane proteins are sorted into different, specialized domains of the cell surface and how this process affects intestinal formation. Additionally, Daniel studies how inflammation is evaded in intestinal epithelial cells in Crohn’s disease using a combination of patient biopsy samples and animal studies in zebrafish. This project is a collaborative effort aided by clinicians and human geneticists at the Duke University Medical Center.

A microscope image of a zebrafish gut

The developing gut of a zebrafish, magnified.

Though complex human diseases can’t be fully mimicked in animal models like zebrafish, this type of research can be extremely useful. These model organisms can be used to study the basic, fundamental cellular mechanisms that ultimately underlie disease. An example is Daniel’s work on Crohn’s disease, where he is trying to understand how inflammatory signaling networks become activated, specifically in intestinal epithelial cells. This problem is difficult, if not impossible, to address using exclusively human biopsy samples.

Overall, Daniel hopes that his translational research will provide new knowledge of the role of intestinal epithelial cells in Crohn’s disease and provide biomarkers that will aid clinicians in predicting how patients will respond to therapeutic interventions. Daniel’s research and basic science research are rapidly changing the way we diagnose disease, treat patients, and interact with the world around us.

Guest post by Vaishnavi Siripurapu

From Solid to Liquid and Back Again

A black and white moving image of a ball being pulled out from under a pile of circular discs

Force chains erupt as an “intruder” is yanked from beneath a pile of circular discs, which are designed to simulate a granular material. The entire process takes less than one second. Credit: Yue Zhang, Duke University.

You can easily walk across the sand on a beach. But step into a ball pit, and chances are you’ll fall right through.

Sand and ball pits are both granular materials, or materials that are made of collections of much smaller particles or grains. Depending on their density and how much force they experience, granular materials sometimes behave like liquids — something you fall right through — and sometimes “jam” into solids, making them something you can stand on.

“In some cases, these little particles have figured out how to actually form solid-like structures,” said Robert P. Behringer, James B. Duke Professor of Physics. “So why don’t they always just go squirting sideways and relax all the stress?”

Physicists do not yet understand exactly when and how jamming occurs, but Behringer’s team at Duke is on the case. The group squishes, stretches, hits, and pulls at granular materials to get a better picture of how and why they behave like they do. The team recently presented a whopping 10 papers at the 2017 Powders and Grains Conference, which occurred from July 3-7, 2017 in Montpellier, France.

Many of these studies use one of the lab’s favorite techniques, which is to create granular materials from small transparent discs that are about half an inch to an inch in diameter. These discs are made of a material which, thanks to the special way it interacts with light, changes color when squished. This effect allows the team to watch how the stress within the material changes as various forces are applied.

A blue and green moving image of spinning discs

As the wheels turn, shear strain between the discs creates a dense web of inter-particle forces. Credit: Yiqiu Zhao, Duke University.

In one experiment, graduate student Yue Zhang used a high-speed camera to catch the stress patterns as a ball on a string is yanked out from a pile of these discs. In the video, the ball first appears to be stuck under the pile, and then suddenly gives way after enough force is applied — not unlike what you might experience pulling a tent stake out of the ground, or opening the lid on a pesky pickle jar.

“The amusing thing is that you start trying to pull, you add more force, you add more force, and then at some point you pull so hard that you hit yourself in the head,” Behringer said.

The team was surprised to find that the stress patterns created by the ball, which Behringer says look “like hair all standing on end,” are almost identical to the stress of impact, only in reverse.

“What you see is even though you are just gradually gradually pulling harder and harder, the final dynamics are in some sense the same dynamics that you get on impact,” Behringer said.

In another experiment, the team examined what happens in granular materials under shear strain, which is similar to the force your fingers exert on one another when you rub them together.

Graduate student Yiqiu Zhao placed hundreds of these discs onto a circular platform made of a series of flat, concentric rings, each of which is controlled by a separate motor. As the rings turn at different speeds, the particles rub against one another, creating a shear stress.

An image of an experimental set up in a lab

Beneath the small transparent discs lie a series of concentric wheels, each attached to its own motor. By turning these platforms at different speeds, Yiqiu Zhao can observe how shear strain affects the discs.

“We have about twenty stepper motors here, so that we can rotate all the rings to apply a shear not only from the outside boundary, but also from everywhere inside the bulk of the material,” Zhao said. This ensures that each particle in the circle experiences a similar amount of shear.

“One of the key intents of this new experiment was to find a way that we could shear until the cows come home,” Behringer said. “And if it takes a hundred times more shear than I could get with older experiments, well we’ll get it.”

As the rings turn, videos of the material show forces snaking out from the inner circle like lightning bolts. They found that by applying enough shear, it is possible to make the material like a solid at much lower densities than had been seen before.

“You can actually turn a granular fluid into a granular solid by shearing it,” Behringer said. “So it is like you don’t put your ice in the refrigerator, you put it in one of these trays and you shear the tray and it turns into ice.”

Kara J. Manke, PhDPost by Kara Manke

3D Virus Cam Catches Germs Red-Handed

A 3D plot of a virus wiggling around

The Duke team used their 3D virus cam to spy on this small lentivirus as it danced through a salt water solution.

Before germs like viruses can make you sick, they first have to make a landing on one of your cells — Mars Rover style — and then punch their way inside.

A team of physical chemists at Duke is building a microscope so powerful that it can spot these minuscule germs in the act of infection.

The team has created a new 3D “virus cam” that can spy on tiny viral germs as they wriggle around in real time. In a video caught by the microscope, you can watch as a lentivirus bounces and jitters through an area a little wider that a human hair.

Next, they hope to develop this technique into a multi-functional “magic camera” that will let them see not only the dancing viruses, but also the much larger cell membranes they are trying breech.

“Really what we are trying to investigate is the very first contacts of the virus with the cell surface — how it calls receptors, and how it sheds its envelope,” said group leader Kevin Welsher, assistant professor of chemistry at Duke. “We want to watch that process in real time, and to do that, we need to be able to lock on to the virus right from the first moment.”

A 3D plot spells out the name "Duke"

To test out the microscope, the team attached a fluorescent bead to a motion controller and tracked its movements as it spelled out a familiar name.

This isn’t the first microscope that can track real-time, 3D motions of individual particles. In fact, as a postdoctoral researcher at Princeton, Welsher built an earlier model and used it to track a bright fluorescent bead as it gets stuck in the membrane of a cell.

But the new virus cam, built by Duke postdoc Shangguo Hou, can track particles that are faster-moving and dimmer compared to earlier microscopes. “We were trying to overcome a speed limit, and we were trying to do so with the fewest number of photons collected possible,” Welsher said.

The ability to spot dimmer particles is particularly important when tracking viruses, Welsher said. These small bundles of proteins and DNA don’t naturally give off any light, so to see them under a microscope, researchers first have to stick something fluorescent on them. But many bright fluorescent particles, such as quantum dots, are pretty big compared to the size of most viruses. Attaching one is kind of like sticking a baseball onto a basketball – there is a good chance it might affect how the virus moves and interacts with cells.

The new microscope can detect the fainter light given off by much smaller fluorescent proteins – which, if the virus is a basketball, are approximately the size of a pea. Fluorescent proteins can also be inserted to the viral genome, which allows them to be incorporated into the virus as it is being assembled.

“That was the big move for us,” Welsher said, “We didn’t need to use a quantum dot, we didn’t need to use an artificial fluorescent bead. As long as the fluorescent protein was somewhere in the virus, we could spot it.” To create their viral video, Welsher’s team enlisted Duke’s Viral Vector Core to insert a yellow fluorescent protein into their lentivirus.

Now that the virus-tracking microscope is up-and-running, the team is busy building a laser scanning microscope that will also be able to map cell surfaces nearby. “So if we know where the particle is, we can also image around it and reconstruct where the particle is going,” Welsher said. “We hope to adapt this to capturing viral infection in real time.”

Robust real-time 3D single-particle tracking using a dynamically moving laser spot,” Shangguo Hou, Xiaoqi Lang and Kevin Welsher. Optics Letters, June 15, 2017. DOI: 10.1364/OL.42.002390

Kara J. Manke, PhDPost by Kara Manke

Cooking Up “Frustrated” Magnets in Search of Superconductivity

Sara Haravifard

A simplified version of Sara Haravifard’s recipe for new superconductors, by the National High Magnetic Field Laboratory

Duke physics professor Sara Haravifard is mixing, cooking, squishing and freezing “frustrated” magnetic crystals in search of the origins of superconductivity.

Superconductivity refers to the ability of electrons to travel endlessly through certain materials, called superconductors, without adding any energy — think of a car that can drive forever with no gas or electricity. And just the way gas-less, charge-less cars would make travel vastly cheaper, superconductivity has the potential to revolutionize electronics and energy industry.

But superconductors are extremely rare, and are usually only superconductive at extremely cold temperatures — too cold for any but a few highly specialized applications. A few “high-temperature” superconductors have been discovered, but scientists are still flummoxed at why and how these superconductors exist.

Haravifard hopes that her magnet experiments will reveal the origins of high-temperature superconductivity so that researchers can design and build new materials with this amazing property. In the process, her team may also discover materials that are useful in quantum computing, or even entirely new states of matter.

Learn more about their journey on this fascinating infographic by The National High Magnetic Field Laboratory.

Infographic describing magnetic crystal research

Infographic courtesy of the National High Magnetic Field Laboratory

Kara J. Manke, PhD

Post by Kara Manke

Students Share Research Journeys at Bass Connections Showcase

From the highlands of north central Peru to high schools in North Carolina, student researchers in Duke’s Bass Connections program are gathering data in all sorts of unique places.

As the school year winds down, they packed into Duke’s Scharf Hall last week to hear one another’s stories.

Students and faculty gathered in Scharf Hall to learn about each other’s research at this year’s Bass Connections showcase. Photo by Jared Lazarus/Duke Photography.

The Bass Connections program brings together interdisciplinary teams of undergraduates, graduate students and professors to tackle big questions in research. This year’s showcase, which featured poster presentations and five “lightning talks,” was the first to include teams spanning all five of the program’s diverse themes: Brain and Society; Information, Society and Culture; Global Health; Education and Human Development; and Energy.

“The students wanted an opportunity to learn from one another about what they had been working on across all the different themes over the course of the year,” said Lori Bennear, associate professor of environmental economics and policy at the Nicholas School, during the opening remarks.

Students seized the chance, eagerly perusing peers’ posters and gathering for standing-room-only viewings of other team’s talks.

The different investigations took students from rural areas of Peru, where teams interviewed local residents to better understand the transmission of deadly diseases like malaria and leishmaniasis, to the North Carolina Museum of Art, where mathematicians and engineers worked side-by-side with artists to restore paintings.

Machine learning algorithms created by the Energy Data Analytics Lab can pick out buildings from a satellite image and estimate their energy consumption. Image courtesy Hoël Wiesner.

Students in the Energy Data Analytics Lab didn’t have to look much farther than their smart phones for the data they needed to better understand energy use.

“Here you can see a satellite image, very similar to one you can find on Google maps,” said Eric Peshkin, a junior mathematics major, as he showed an aerial photo of an urban area featuring buildings and a highway. “The question is how can this be useful to us as researchers?”

With the help of new machine-learning algorithms, images like these could soon give researchers oodles of valuable information about energy consumption, Peshkin said.

“For example, what if we could pick out buildings and estimate their energy usage on a per-building level?” said Hoël Wiesner, a second year master’s student at the Nicholas School. “There is not really a good data set for this out there because utilities that do have this information tend to keep it private for commercial reasons.”

The lab has had success developing algorithms that can estimate the size and location of solar panels from aerial photos. Peshkin and Wiesner described how they are now creating new algorithms that can first identify the size and locations of buildings in satellite imagery, and then estimate their energy usage. These tools could provide a quick and easy way to evaluate the total energy needs in any neighborhood, town or city in the U.S. or around the world.

“It’s not just that we can take one city, say Norfolk, Virginia, and estimate the buildings there. If you give us Reno, Tuscaloosa, Las Vegas, Pheonix — my hometown — you can absolutely get the per-building energy estimations,” Peshkin said. “And what that means is that policy makers will be more informed, NGOs will have the ability to best service their community, and more efficient, more accurate energy policy can be implemented.”

Some students’ research took them to the sidelines of local sports fields. Joost Op’t Eynde, a master’s student in biomedical engineering, described how he and his colleagues on a Brain and Society team are working with high school and youth football leagues to sort out what exactly happens to the brain during a high-impact sports game.

While a particularly nasty hit to the head might cause clear symptoms that can be diagnosed as a concussion, the accumulation of lesser impacts over the course of a game or season may also affect the brain. Eynde and his team are developing a set of tools to monitor both these impacts and their effects.

A standing-room only crowd listened to a team present on their work “Tackling Concussions.” Photo by Jared Lazarus/Duke Photography.

“We talk about inputs and outputs — what happens, and what are the results,” Eynde said. “For the inputs, we want to actually see when somebody gets hit, how they get hit, what kinds of things they experience, and what is going on in the head. And the output is we want to look at a way to assess objectively.”

The tools include surveys to estimate how often a player is impacted, an in-ear accelerometer called the DASHR that measures the intensity of jostles to the head, and tests of players’ performance on eye-tracking tasks.

“Right now we are looking on the scale of a season, maybe two seasons,” Eynde said. “What we would like to do in the future is actually follow some of these students throughout their career and get the full data for four years or however long they are involved in the program, and find out more of the long-term effects of what they experience.”

Kara J. Manke, PhD

Post by Kara Manke

Mental Shortcuts, Not Emotion, May Guide Irrational Decisions

If you participate in a study in my lab, the Huettel Lab at Duke, you may be asked to play an economic game. For example, we may give you $20 in house money and offer you the following choice:

  1. Keep half of the $20 for sure
  2. Flip a coin: heads you keep all $20; tails you lose all $20

In such a scenario, most participants choose 1, preferring a sure win over the gamble.

Now imagine this choice, again starting with $20 in house money:

  1. Lose half of the $20 for sure
  2. Flip a coin: heads you keep all $20; tails you lose all $20

In this scenario, most participants prefer the gamble over a sure loss.

If you were paying close attention, you’ll note that both examples are actually numerically identical – keeping half of $20 is the same as losing half of $20 – but changing whether the sure option is framed as a gain or a loss results in different decisions to play it safe or take a risk. This phenomenon is known as the Framing Effect. The behavior that it elicits is weird, or as psychologists and economists would say, “irrational”, so we think it’s worth investigating!

Brain activity when people make choices consistent with (hot colors) or against (cool colors) the Framing Effect.

Brain activity when people make choices consistent with (hot colors) or against (cool colors) the Framing Effect.

In a study published March 29 in the Journal of Neuroscience, my lab used brain imaging data to test two competing theories for what causes the Framing Effect.

One theory is that framing is caused by emotion, perhaps because the prospect of accepting a guaranteed win feels good while accepting a guaranteed loss feels scary or bad. Another theory is that the Framing Effect results from a decision-making shortcut. It may be that a strategy of accepting sure gains and avoiding sure losses tends to work well, and adopting this blanket strategy saves us from having to spend time and mental effort fully reasoning through every single decision and all of its possibilities.

Using functional magnetic resonance imaging (fMRI), we measured brain activity in 143 participants as they each made over a hundred choices between various gambles and sure gains or sure losses. Then we compared our participants’ choice-related brain activity to brain activity maps drawn from Neurosynth, an analysis tool that combines data from over 8,000 published fMRI studies to generate neural maps representing brain activity associated with different terms, just as “emotions,” “resting,” or “working.”

As a group, when our participants made choices consistent with the Framing Effect, their average brain activity was most similar to the brain maps representing mental disengagement (i.e. “resting” or “default”). When they made choices inconsistent with the Framing Effect, their average brain activity was most similar to the brain maps representing mental engagement (i.e. “working” or task”). These results supported the theory that the Framing Effect results from a lack of mental effort, or using a decision-making shortcut, and that spending more mental effort can counteract the Framing Effect.

Then we tested whether we could use individual participants’ brain activity to predict participants’ choices on each trial. We found that the degree to which each trial’s brain activity resembled the brain maps associated with mental disengagement predicted whether that trial’s choice would be consistent with the Framing Effect. The degree to which each trial’s brain activity resembled brain maps associated with emotion, however, was not predictive of choices.

Our findings support the theory that the biased decision-making seen in the Framing Effect is due to a lack of mental effort rather than due to emotions.

This suggests potential strategies for prompting people to make better decisions. Instead of trying to appeal to people’s emotions – likely a difficult task requiring tailoring to different individuals – we would be better off taking the easier and more generalizable approach of making good decisions quick and easy for everyone to make.

Guest post by Rosa Li

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