Research Blog

Student Cameron Kim, Working to Reprogram Cells

On October 8, 2012

In Biology, Biomedical Engineering, Engineering, Students

By Nonie Arora

Meet Cameron Kim – a Pratt Engineering student working on synthetic biology who also officiates for the Duke Quidditch team. Originally from Brandon, Florida, Cameron became interested in molecular biology and engineering in high school.

Kim Observing His DNA Gel Credit: Cameron Kim

“I see most people identify biomedical engineering as biomechanics, neural engineering, and electrophysiology,” he says, “but there’s really this other side growing quicker and quicker, which is using the tools of molecular biology to control how we as humans function and interact with the environment.”

In Dr. Charles Gersbach’s lab, he has been working to create artificial transcription factors. Being able to control gene expression through transcriptional factors is vital to modulate cell behavior and human functions, Kim says.

Kim drew an analogy between a transcription factor and a light switch dimmer, saying that transcription factors allow for a range when turning on and off specific genes. He says that artificial transcription factors would allow him to influence a cell’s own genome without having to add extra copies of a gene. The goal is to develop a tool to reprogram cells that his lab can use to study muscle development and to hopefully repair muscles. His lab is looking at different ways to develop therapies for Duchenne muscular dystrophy.

Kim thinks that engineering design principles that he has learned through his Pratt coursework are really important to his project. “When I explain my research to a lot of people, they think I’m just doing molecular biology,” he says, “but by knowing the parts and understanding my materials, I can design biological molecules and tools do what I want them to do.” While we may traditionally associate engineers observing factors like the terrain or landscape to build a bridge, he looks at factors like energy barriers and cell functions to apply design principles to molecular biology.

Kim Presenting at the Howard Hughes Research Symposium Credit: Cameron Kim

Research is full of challenges, and Kim’s projects have been no exception. He says it has been challenging to develop his tool. While it looks great in one test, it does not work with another one. He is still investigating whether he should be looking for other factors to control or whether the challenges are due to biological limits.

When asked what advice he would give to other undergrads excited about delving into research, Kim said to recognize that “you’re not going to know everything and even brightest minds in the field don’t know everything,” and to also “find out more about whatever you’re interested and take advantage of wide base of knowledge around you.”

His project initially came out of the Howard Hughes Research Fellows Program, which he encourages first-year students to consider. Kim says, “An immersion program in research can be a just as exciting new environment as an immersion language program in another country.”

After Duke, Kim hopes to pursue medical research. He wants to ask questions like: “How can I bridge the gap from bench to bedside? What tools can I develop to reach a clinical applications?” He feels lucky to have been mentored by excellent scientists and would like to do the same for others in the future.

Third Mahato Viz Contest, Deadline Oct. 21

By Karl Bates

On October 3, 2012

In Engineering, Science Communication & Education, Visualization

2011 People's Choice "Cold Atom Cloud," by Yinghi Zhang - Duke Graduate Student in Physics

Nearly 5 years after the tragic death of engineering graduate student Abhijit Mahato, the Duke community will once again honor his memory with a photography and visualization contest.

Deadline for entries is October 21, 2012. Rules are here: http://mahato.pratt.duke.edu/contest

This year’s awards ceremony and exhibit of entries will be Nov. 7 at 5 p.m. in Schiciano Auditorium. The keynote speaker at this year’s event will be Kellar Autumn, professor and chair of biology at Lewis & Clark College, who led a research team that discovered the trick gecko feet use to stick to any surface without an adhesive.

The first two contests produced a spectacular collection of beautiful images from scientific research to exotic locations to mundane objects like lightbulbs and jelly glasses viewed in startling new ways.

Learn More: http://mahato.pratt.duke.edu/

Crossing the Valley of Death

By sa160@duke.edu

On October 3, 2012

In Business/Economics, Cancer, Lecture, Medicine

By Nonie Arora

David Adams shared his concerns about the output of America’s drug development pipeline at last month’s Science and Society Journal Club at the Institute for Genome Science and Policy (IGSP).

When it costs more than $1 billion to bring a drug to market with many failures along the way, “many (drug) companies are focused on de-risking,” according to Adams, an Associate Professor of Medicine in the Division of Medical Oncology.

Adams said the pharmaceutical industry seems to be counting on biotech companies and academia to help drugs cross the “Valley of Death” in anticancer drug development, but that has yet to happen.

While the rate of publication and quantity of scientific data continue to increase rapidly, not enough funding is being devoted to the “translational” research, which helps an idea make it from the lab to the clinic, Adams said.

Example of a tissue chip project sponsored through NCATS to improve drug safety. Credit to NCATS website.

The pharmaceutical industry has cut down on translational research, Adams said. Essentially, companies don’t want to take on projects unless they have a very high probability of success.

He also said that the National Institutes of Health (NIH) is generally risk adverse and tends to fund projects that represent “the next logical step,” rather than going for higher-risk, but potentially higher-gain ideas. The National Center for Translational Sciences (NCATS), established by the NIH director Francis Collins last year, is a promising step, Adams said.

When researchers design their cancer studies, many times they “don’t really take into account tumor physiology because we live in this era of molecular biology,” Adams said. He believes accounting for tumor physiology is very important. For example, doctors are rarely able to monitor how much drug makes it to a tumor, but translational research could solve this problem, said Adams.

Adams said drug development is also hampered by a human tendency toward “technological lock-in.”

Personal Genome Machine Sequencer Credit: Benchmarks, a publication of the National Cancer Institute

“Why do we not change the way that we do things when there is compelling evidence to do so?” He argued that:

1) people resist change in research and clinical environments because they are creatures of habit and convenience,

2) academics and clinicians often operate in silos rather than multidisciplinary teams that would enhance communication, and

3) we are obsessed with technology, as evidenced by genomics.

Adams said a new area to watch out for is theranostics: compounds that combine a therapeutic and diagnostic in the same formulation. Another area is miniaturization of electronics to permit real-time measurement of drug activity in and around tumors. An implantable radiation dose monitoring system is already commercially available and implantable sensors for management of diabetes are in the pipeline.

Ultimately, greater emphasis on translational research and breaking technological and organizational lock-in may help us cross this “Valley of Death,” he said.

Packing for Proteins

By Ashley Yeager

On September 27, 2012

In Biology, Chemistry, Physics

This artist's rendering shows a ribbon diagram of the protein T4 phage lysozyme. Image courtesy of Ohio State.

By Ashley Yeager

If you ask vacationers about packing, they’ll probably tell you about over-stuffed suitcases and inflatable beach toys. But if you ask Yale physicist Corey O’Hern, he’ll tell you packing is about pockets, proteins and geometry.

“You may not believe it or may not have heard about it, but I’m going to argue that just geometry is important for understanding protein structure,” and “that makes protein structure look like a packing problem,” O’Hern said at a Sept. 26 physics colloquium. The protein packing problem and solving it could have implications for drug design.

O’Hern first learned about packing problems in physics as an undergraduate at Duke in the early 1990s. Working with Duke physicist Bob Behringer, he tried to explain how corn and coffee beans get jammed in their dispensers. O’Hern continued this type of work as a graduate student at the University of Pennsylvania and then earned a faculty post as a theorist in Yale’s engineering and applied science department.

“I didn’t believe in fate until I went to Yale and learned about Fred Richards. Now I do,” O’Hern said, explaining that the Yale biophysicist was interested in the structure of proteins and the “interior packing,” or arrangement, of their amino acids. O’Hern said Richards thought of proteins as a jigsaw puzzle and tried to figure out how the weird pieces fit together.

To better understand a protein’s geometry, Richards would trace water molecules over the surface of its amino acids. He thought that the inner folds of proteins were “well-packed” because the strong attractions of the atoms in those areas. “I don’t completely believe Richards’ results,” but the work “made me feel destined to get in on the research,” O’Hern said.

He now looks at how tightly animo acid molecules fit together in certain regions of the protein, T4 phage lysozyme. To study its packing properties, O’Hern simulates the energy and entropy in the pockets, or cavities, of the lysozyme’s inner folds. His early results suggest that the most stable forms of the protein have the most entropy, or randomness, among the amino acids in the pockets.

That way of packing is definitely counter-intuitive, O’Hern said. He’s still working on how the results are possible and, in a broader sense, how they could affect packing and folding of drugs to improve their effectiveness.

A "Neurodiverse" View of Poetry

By Ashley Mooney

On September 26, 2012

In Behavior/Psychology, Faculty, Science Communication & Education

By Ashley Mooney

Why is an English professor working with brain scientists? To change our understanding of the interaction between autism and poetry.

Autism spectrum disorder is often characterized by an inability to comprehend figurative language, especially metaphors. But poet Ralph Savarese, an associate professor of English at Grinnell College currently doing a residency with the Duke Institute for Brain Sciences as a Mellon Humanities Writ Large Fellow, has found the exact opposite to be true in his interactions with people who have autism.

“One of the supposed symptoms of autism is an inability to deal with figurative language—metaphor, simile, irony, jokes—and what I can tell you is, it is not true about certain autistic subtypes, particularly literate classical autistics,” he said.

Literate classical autistics are the most severely autistic, and often nonspeaking. Savarese, who also teaches creative writing workshops to people with autism, noted that although it often takes years to teach these people how to read, once learned “there is absolutely no failure of figurative knowledge, indeed just the opposite is enormous sensitivity to metaphor [and] simile.”

Poetry is not abstract, but rather is about the concrete particulars of life, Savarese said, which lines up nicely with an autistic neurology. He noted that poetry or lyrical language could serve as a neurocosmopolitan meeting place. Neurocosmopolitanism means to be comfortable with various neurologies.

“What would [neurocosmopolitanism] mean as a doctor or as an English professor who might have somebody with autism in his classroom?” he asked. “It’s not just that I’m demanding that autistics learn how we do things, it’s that we learn how they do things.”

What would it mean to be comfortable with all matter of neurologies, what would it mean to find common ground or talk or find a way to communicate respectfully with somebody whose brain is different, he added.

Rather than seeing disability as “an occasion for pity or demonization,” Savarese instead reframes autism as a type of neurodiversity—a neurological difference.

“For the last 30 years we’ve had this notion of diversity drilled into us, why not neurodiversity,” he said. “It’s true that autistics can do some things better than us and some things worse than us.”

Unlike 30 years ago, there are now many people who have autism across the spectrum who have written about their experiences, he said. With a large volume of literature at hand, people can now familiarize themselves with both the traditional medical view from an outsider’s perspective and insider accounts. He added that people should familiarize themselves with both because they generate different notions of the world.

Savarese has a personal connection to autism. His adopted son DJ is nonspeaking autistic who types to communicate. DJ, who started school at Oberlin College three weeks ago, is also the first nonspeaking autistic person to ever get into a highly selective college, he said.

“It’s not that I’m unrealistic—I’ve lived with the challenges of autism for 14 years,” Savarese says. “I’m not saying there aren’t significant challenges with autism, but I refuse to describe autism in the way that it has been typically described.”

He noted that although his son has significant motor and communication challenges, his memory and pattern recognition are astonishing. “His memory is photographic, and he’s just like, ‘are you kidding me, you all are retarded.’”

Savarese noted that the struggle in how to treat people with autism was exemplified in an interview that his son did. In the interview, he was asked if autism should be treated, and DJ typed in response, “yes, treated with respect.”

Although the most famous disability rights adage is “nothing about us without us,” he said, adding that there is a division between the literature written by autistics and scientific research that rarely makes an appeal to those with autism.

“What you see is somebody a lot like you or me going to some other culture that is very different from our own and insisting that culture operate the way that ours does,” he said. “Almost everything that I stand for is in opposition to many of the ideas [of what autism is] and the ways in which the ideas have been propagated. There is this idea autistics have no awareness of the self or others…. I just don’t buy it.”

Taking a 'DiVE' into Neutrinos

By Ashley Yeager

On September 21, 2012

In Physics, Science Communication & Education, Visualization

Physicists can now analyze neutrino events, such as this one, in 3D. Courtesy: Berkeley Lab.

By Ashley Yeager

Using a virtual, 3D environment, scientists are getting their closest look yet at neutrinos’ interactions with matter.

Neutrinos are subatomic particles that “interact with matter only very rarely, maybe once in your body in your entire lifetime,” said Duke physicist Kate Scholberg during a Sept. 21 talk, which the Visualization Technology Group hosted.

Scholberg explained that to study neutrino interactions, scientists use large, underground detectors, which may only record one event per day. That might not seem significant. But, as Scholberg explained, scientists need to observe the events to determine how the universe developed with more matter than anti-matter, a phenomenon that allows life to exist.

Typically, Scholberg and her colleagues analyze neutrino interactions from their Japan-based detector Super-K in a two-dimensional computer program. Recently, however, Scholberg “stepped” into the Duke immersive Virtual Environment, or DiVE, a six-sided, cave-like, virtual-reality theater programed with data from Super-K.

Inside, Scholberg got her first look at neutrinos interactions in 3D. She was able to see a representation of Super-K and thousands of its light detectors. She could also see data from a recent neutrino event and was able to walk around the detector simulation and visualize the neutrino interaction from all sides. The software had even traced out the “sonic boom” of light, which looks like a circle in two-dimensions and a cone or ring in three-dimensions, given off after a neutrino event.

“This is what I’ve imagined happens a million times after an interaction,” Scholberg said, showing a video of her experience in the DiVE. “It’s entirely different seeing it in 3D,” she said, adding that the drawing of the cone shape of a Cherenkov ring has never been done in a neutrino event display before.

Benjamin Izatt a student at the University of California, Berkeley was the mastermind who developed the 3D neutrino simulation, called Super-KAVE. He designed it to help Duke physicists explain their neutrino research to the public.

But, Scholberg said, the tool may also help her and her collaborators at Super-K better understand complex neutrino interactions and sort out where the particles’ rings and cones overlap. She added that in future simulations, “we may also be able to see particles and interact with the particles, which would be not only fun, but helpful.”

Igniting U.S. health care's 'escape fire'

By Ashley Yeager

On September 21, 2012

In Behavior/Psychology, Cancer, Cardiology, Genetics/Genomics, Global Health, Medicine

The film Escape Fire explores what's fanning the flames of the health care debate. Credit: escapefiremove.com

By Ashley Yeager

Imagine lighting a match to protect yourself from the flames of a fire.

It’s probably not the first thing you would think to do to stop from being burnt. But when there’s no other escape, the technique works. In 1949, Robert Wagner Dodge became living proof when he lived through the Mann Gulch fire by setting his surroundings on fire.

Now, his actions have become a metaphor for drastic ways government and industry should change U.S. health care before it too burns everything in its path.

Escape Fire: The Fight to Rescue American Healthcare showcases the health care system’s metaphorical blaze. The award-winning documentary, described as the “Inconvenient Truth” of the health care debate, opens nationwide in October. But members of the Duke community saw it for free on Wed., Sept. 19. They were also able to participate in a post-film panel discussion, which fleshed out a few potential escape fires for the health care industry.

“I think working with one patient at a time can help everyone become healthier,” said Annie Nedrow, a primary care physician and the associate director of Duke Integrative Medicine, which sponsored the event. But as the film points out, the current system rewards doctors for the number of patients they see, not the amount of time they spend with each person or the plans they may develop to help that patient prevent and manage disease.

Ironically, almost 75 percent of health care costs are spent on preventable diseases. The film, directed by Matthew Heineman and Susan Froemke, illustrates this statistic through anecdotes, where a band-aide, pill or even invasive surgery, such as inserting a stent to relieve heart blockages, provides immediate relief but does nothing to address the underlying causes of illnesses – typically diet and lifestyle.

Preventable diseases are 75% of our health care costs. Credit: escapefiremovie.com

“There’s got to be a shift in our culture, one where we actually have access to safe parks to exercise, healthy food, and the time to eat it,” said Adam Perlman, Duke Integrative Medicine’s executive director. He also agreed with Nedrow that a new system should invest more in primary care and health promotion, rather than disease treatment.

To set an example and test the feasibility of such a system, Duke Integrative Medicine has opened a primary care practice that limits the number of patients each physician sees so the doctors can spend more time with each patient and create a more holistic approach to that person’s health.

Perlman said that health coaching could be another important aspect of correcting the healthcare system. He explained that doctor X might tell a patient to lower his blood sugar, doctor Y then tells him to lower his blood pressure, and all the patient really wants to do is dance at his daughter’s wedding. “A health coach helps the patient reach those bigger goals by connecting the dots and helps them execute the plan to get there,” he said.

The film and remarks prompted many audience members to question what it would take to change the current system. Nedrow, who said she has been inspired by books on creativity and innovation, suggested that it was dialogues like the one they were having that could ignite change to repair the broken model of health care or create a new system.

More innovation, however, may mean that more people need to step into the fire and strike a match, rather than run and try to dodge the flames.

Football Player Makes an Impact

By Ashley Mooney

On September 19, 2012

In Biomedical Engineering, Medicine, Students

by Ashley Mooney

One Duke football player is making an impact, both on and off the field, on the health of his teammates.

Senior Conor Irwin, an evolutionary anthropology major who is also an offensive lineman on the varsity football team, has done research regarding joint replacements and athletic injuries during his time at Duke.

In summer 2011, Irwin worked at the K-Lab, which focuses on understanding and preventing athletic injuries. There, he studied pressure distribution on the foot during unanticipated cutting—a maneuver where the person changes directions quickly.

To test this, subjects wore pressure sensor insoles in their shoes to show the distribution of stress in their feet during the task, which involved running in a straight line and then planting and cutting in the direction of a flashing light.

Irwin also collected data on hip, knee and ankle replacement patients who came into the lab for evaluations.

“As I understood it, Duke is one of few institutions to perform ankle replacements, and this [data] was being used to evaluate the different surgical techniques for ankle replacement,” Irwin said.

Beyond his work in the K-Lab, Irwin conducted an independent study with the advice of Dr. Claude Moorman III, director of the Duke Sports Medicine Center and head team physician, and John Anderson, a sports medicine fellow. He reviewed different surgical techniques for repairing a ruptured medial collateral ligament in the knee.

“The frequency of MCL injuries in football players—particularly offensive linemen, which is what I play—made me interested in a project dealing with the MCL,” he said.

MCL ruptures do not often require surgical interventions, however, there are certain cases where it is necessary. Irwin studied the progression of MCL treatments as well as current techniques.

Although the paper is still in the editing stage, Irwin noted that they plan to submit it to the Journal of the American Academy of Orthopaedic Surgeons. They will also submit a video of an MCL operation on a cadaver as a separate publication.

Monkey Marketing and Poop-Dodging

By Ashley Mooney

On September 12, 2012

In Animals, Behavior/Psychology, Business/Economics, Neuroscience, Students

by Ashley Mooney

Have you ever thought of advertising to a monkey?

Junior Yavuz Acikalin, an economics and neuroscience double major, is doing an independent research project with the Platt Lab that deals with just that—monkey advertising. Acikalin’s project deals with whether or not one can influence primate reward preferences by branding rewards. Branding involves using associations between brand logos and images of female monkey perinea—“sexy images” for monkeys in his words—and high status male faces.

“Finding similarities between how mainstream methods of marketing affect humans and monkeys can lead to a better understanding of the evolutionary factors that affect consumer behavior,” he said. “Experiments on monkeys can help us better understand the irrationalities that happen in the markets, and more importantly, the brain mechanisms that underlie the effects of advertising on consumer behavior.”

The lab, run by Michael Platt, director of the Duke Institute for Brain Sciences and Center for Cognitive Neuroscience, studies how the brain decides between different actions. A main focus of the lab is on value-based decision making, and the brain mechanisms responsible for these processes—in summary, neuroeconomics, Acikalin said.

His daily duties include writing Matlab code for the touch-screen interface that the monkeys use, he said. He also writes code for data analysis and runs the experiments.

Acikalin noted that he loves animals and cannot live without having multiple pets at home, making his time with the monkeys rewarding. His research, however, does come with its downsides.

“My least favorite part is dealing with all the biohazard on a daily basis—or more precisely, monkey poop,” he said.

A Different Kind of "Knock Out Mouse"

By Ashley Mooney

On August 30, 2012

In Animals, Behavior/Psychology, Neuroscience, Students

by Ashley Mooney

What is the best method to test anxiety in mice? I spent my summer at home in Portland, Ore. figuring out just that.

According to the National Institute of Mental Health, one in five adults in the United States have an anxiety disorder, but only about a third of those people are receiving treatment. In order to develop better medications, we wanted to understand the mechanism by which injuries—such as traumatic brain injury—lead to anxiety disorders.

The "guillotine" I helped build to model traumatic brain injury in mice

The lab was using six tests on mice, including the elevated plus maze, acoustic startle response and the “hyponeophagia test”—which examined how long it took a mouse to consume a new food. My boss, a postdoctoral researcher, ran a series of correlations on test results to find that some are not as effective in testing anxiety as scientific journals say they are.

I helped build two of the other tests that were new to the lab. One of them was a guillotine of sorts to test traumatic brain injury. While the guillotine does not do anything gruesome to the mice, it does give them a minor concussion to model the type of injury that many people experience in sports, car accidents and other mishaps.

We were looking at whether traumatic brain injury increases your chance of developing anxiety. To do this, we conditioned 80 mice and put them through mazes before and after knocking them on the head.

Although the mice kept me pretty busy, the head veterinarian of the research institute allowed me to shadow him in the mornings and help out with the pigs and rodents.

And a lesson from all of my maze-building experiences: chloroform is useful for more than knocking people unconscious—one can use it to bind plastic together and create a plethora of fun experiments for mice to run around.