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

Students exploring the Innovation Co-Lab

Author: Ashley Mooney Page 2 of 3

Tracking the cell transitions that cause cancer

By Ashley Mooney

Courtesy of Tristan Bepler.

Researchers think that for cancer to develop, damaged cells have to undergo certain transitions that cause them to spread, or metastasize.

Junior Tristan Bepler, a biology and computer science major, is testing this hypothesis, studying two types of cell transitions scientists have linked to the spread of cancer. He works in the lab of Mariano Garcia-Blanco, professor of molecular genetics and microbiology, and looks at the mesenchymal-to-epithelial transition, or MET, and the epithelial-to-mesenchymal transition, or EMT. Mesenchymal cells are more motile, while epithelial cells tend to be fixed in rows.

The hypothesis is that when epithelial cells form tumors, like in colon, prostate or breast cancer, the cells at the edge of the tumor have to turn to mesenchymal cells for the cancer metastasize. Then, “the mesenchymal cells can leave the tumor, get into the blood stream and spread around your body,” Bepler said.

In order for cells to latch onto cells in new locations, they have to transition back to epithelial cells through MET. Bepler’s research focuses on whether MET or EMT are necessary for metastasis.

Most of Bepler’s daily activities involve culturing cells and handling the rats the lab uses in for the research.

The scientists grow tumors in the rats, they inject them under the skin on their flank. “When we’re growing tumors, we have to measure the size of the tumors and weigh the rats to make sure they’re not gaining too much weight,” Bepler said. “Once the tumors get too large, we have to sacrifice the rats and dissect them. We collect their tumors and their lungs, then we can section them and look at fluorescence, which is how we track MET and EMT.”

Although the project is in the basic sciences, it has the potential for clinical use. If EMT is necessary for diseased cells to spread, drugs that block the transition may be effective in treating certain types of cancer. Clinical application is still a long way down the road, though, Bepler said.

Choosing to study metastasis, rather than viruses, which the lab also investigates, “really wasn’t driven by a desire to study cancer at the time,” Bepler said. “I really didn’t know anything, so I decided I would do the cancer side.”

A Durham, N.C. native, Bepler began his lab work the summer before his freshman year. “When you first start working in the lab, you basically work as a lab tech. Your mentor says, ‘do this experiment,’ and you do the experiment,” he said. “It’s sometimes hard to feel like what you’re doing is important or like you’re really involved in the project because you’re just working as a lab tech, you’re not intellectually involved.”

“The key is to get into the biology of what’s going on or think about the experiments and then it becomes a lot more interesting, because after a while you come up with good ideas for experiments, and you become a little more independent and can do your own experiments,” he said.

Bepler added that he prefers working with rats, as opposed to mice, because they are more friendly and do not bite as often.

Blasting away glioblastomas

By Ashley Mooney

The purple area of this brain is a glioblastoma tumor.

Some undergraduates get to see the fruits of their lab labor early in their careers.

Junior Anirudh Saraswathula, a biology major and neuroscience minor, has been doing research at Duke since his first week on campus.

He started as a work-study student in professor of cell biology Blanche Capel’s lab, but said the basic sciences were not his true passion. Now, Saraswathula works on translating basic research with the Duke Brain Tumor Immunotherapy Program.

“A lot of what I do in the lab involves looking at protocols that are used in basic science research and trying to apply them to what we’re doing here,” he said. “So a lot of it is going to be culturing cells from patients, and then doing a variety of tests depending on what it is that I want to do.”

He is currently studying immune-system therapy for glioblastoma, a type of malignant brain tumor. By reprogramming a patient’s T-cells, researchers can direct the immune system to fight glioblastoma. Although Saraswathula was not involved in developing the treatment, he is working to evaluate the treatment’s mechanism and its long-term effects on the immune system.

“One of the reasons that brain tumors are so devastating (with treatment they can extend survival to about 18 months) is that they’re just so recurrent,” he said. “These types of tumors also change who you are as a person because of where they happen.”

Saraswathula’s day-to-day work involves culturing tissue, using flow cytometry — a technique used to sort cells, detect biomarkers and engineer proteins — and PCR, which copies DNA.

Saraswathula is also studying the quality of T-cell responses to different clinical trials and understanding whether certain types of B-cells are repressing the function of the tumor vaccine.

“Those projects are focused on future trials. How can we improve, how can we modify these therapies to better improve the immune system’s response in order to fight these tumors,” he said.

Although he began his research just for the experience of doing it, Saraswathula said that applicability is now what is most important to him.

“If I discover some obscure gene in stem cells, there’s not going to be any real application there for maybe 30 years,” he said. “With my current research, if I find something, [in] the next trial a few years from now, there will be a patient getting the drug, and I would have had a contribution to that.”

Grad Student Sees Yawning Gap in Animal Welfare

by Ashley Mooney

Sometimes a middle-school nickname becomes a career.

Graduate student Jingzhi Tan, yawned loudly during a quiet class in middle school in China, garnering the nickname Hippo. So now he’s at Duke, studying yawning behaviors in bonobos.

Jingzhi “Hippo” Tan is a graduate student working on bonobos’ love of strangers.

So-called ‘contagious yawning’ has been found in many species besides humans and other great apes, including baboons, monkeys and dogs. Tan found that bonobos are more likely to yawn along with strangers than they are to yawn with animals they already know. (They also prefer to share food with strangers first.)  In the future, he hopes to do a similar study with chimpanzees, but must first modify the structure of the experiment.

“The bonobo study that we just did is technically unethical to do with chimps—you can’t put two strange chimps together because they’re going to kill each other,” Tan said. “Later we’re trying to develop a task that is chimp-friendly and we’re going to use it for comparison between a variety of species.”

His studies on great apes, he said, will hopefully reveal more about the human mind and aid wildlife conservation efforts.

Tan noted that there is no better way of understanding the human mind than studying its evolution. Through his studies, Tan hopes to uncover the constraints of human problem-solving abilities, which will help solve problems relating to conservation.

“There is a gap between people who want to conserve nature versus people who are making decisions and policies. Usually what they do is alienate each other,” Tan said. “You can’t actually do something unless you really understand the mind of people.”

Likasi, a resident of the Lola ya Bonobo sanctuary in Kinshasa, where Hippo does his work. (Jingzhi Tan)

As an undergraduate at Peking University, Tan studied under the only cognitive evolution professor in all of China. He is now the first Chinese person to study great apes in Africa.

Tan said he is concerned that chimps are apparently being illegally exported to China, where they end up in the entertainment industry. Tan said there is one reality show that features three chimps—dressed in human clothes—choosing fruit at a supermarket. Another pair of infant chimps were forced into a fake wedding, complete with a wedding dress, and received national media attention.

China needs stronger animal welfare laws, Tan said. “Going back to the big picture, in the next decade, if you want to help bonobos in Africa or any other animals in Africa, we have to get China involved. Right now it’s just completely empty and blank.”

The new blood diamond is your cell phone

by Ashley Mooney

There is an African proverb that says “when the elephants fight, the grass suffers.”

In the Democratic Republic of the Congo, the elephants are militias and the grass is the women, said John Prendergast, co-founder of Enough Project, an organization that fights to end genocide.

Congolese rape victims assemble outside of a peace hut. Courtesy of Wikimedia Commons.

Prendergast, who spoke at Duke Nov. 29, said the DRC is now the home of the deadliest war since World War II. The conflict has been created in part by large corporations seeking a variety of natural resources within the region throughout the past 150 years. Currently, the Congo is the main source of gold, tantalum, tin and tungsten, which are used to power electronics such as cell phones, laptops and digital cameras.

“Congo is now the most dangerous war because powerful corporations have come to [the country] for the last few centuries to take whatever they want, and structured the state to facilitate that,” he said. His talk was part of the Ferguson Family Distinguished Lectureship series on the Environment and Society.

The nation is currently riddled by struggles between the Congolese armies, militias and other groups from bordering nations Rwanda and Uganda. Many of the groups utilize brutal tactics throughout mineral-smuggling networks, and, Prendergast said, use sexual violence at the center of their methodology.

“[There has been] no other war in the world where the link between our consumer appetites and sexual violence is so direct,” he said. “All of these groups use rape as a means of social control… They target women to humiliate and destroy the will of the community.”

Prendergast has dedicated himself to the pursuit of peace in the region for over 30 years and has lobbied several companies – including Apple – to use free-trade models of mineral trade.

“Unless international capital or profit-seeking capital is regulated in some way, it will trample all over human rights,” he said.

Prendergast credited Duke’s student body for leading the nation in the Conflict-Free Campus Initiative, which 115 schools are involved in.

The way to create peace, he said, is to pressure the United States government to encourage the United Nations and other countries to support “an African-led peace process in Congo,” which deals with the root causes of the issue.

“We aren’t going to solve all of the Congo’s problems sitting here – we aren’t going to solve them in the United States or Europe,” he said. “But we can play a major role in supporting the Congolese to find those solutions.”

He added that until everyone is more aware of the root cause – the demand for phones, laptops and other electronics – the conflict will not end.

“When you log onto your laptops tonight, remember they wouldn’t be so cheap without minerals from the Congo,” he said. “When you answer your cell phone or make a call, remember… all of the women of the Congo who have survived sexual attacks.

Soft Matter, Or Just Marshmallows?

By Ashley Mooney

When a chemist whisks cake batter, he’s not just thinking about the deliciousness that awaits. Whisking can actually induce chemical reactions integral to the texture of the dessert.

In a class being taught next term, Patrick Charbonneau, assistant professor of chemistry and physics, will help students apply science to creating edible masterpieces. For example, they will make two traditional Quebec desserts as an experiment in phase transitions. The ingredients in both are essentially the same, Charbonneau said, but one requires whisking while the other rests as it cools.

Students will measure the stiffness of marshmallows using chocolate bars, maybe it will end in a gooey s’more.

“By whisking you actually induce micro-crystallization and in the other one you remain in the glass phase, so the texture is completely different,” he said. “They’re going to be cooking—these are real desserts and real recipes—but the science is very controlled.”

Charbonneau works in a sub-discipline of chemistry called “soft matter,” but this doesn’t just mean marshmallows. The subject combines aspects of chemistry, physics, chemical engineering and material sciences—and fits perfectly with the science of cooking.

“The demos [in the class] are centered on food, so one of the cool ones is this material properties experiment measuring the [stiffness] of marshmallows using a chocolate bar,” Charbonneau said. “The chocolate bars are calibrated—you know their weight—and you just need a ruler to measure how much the marshmallow compresses.”

Although Charbonneau usually teaches an advanced physical chemistry course, he said he rediscovered old cuisine—and the science behind it—with the help of his friend from college and chef Justine de Valicourt, who is a visiting artist at Duke. De Valicourt has an undergraduate degree in biomedical sciences, but opted for culinary school rather than medical school. She will teach the cooking components of the seminar.

The class will meet once a week in spring semester for two and a half hours, with the first half dedicated to theory and food-centric demos, followed by cooking experiments and a dinner run by de Valicourt.

While cooking may make science more appealing to the non-scientists at Duke, Charbonneau said a basic understanding of chemistry is required in order to discuss the material in detail.

“Sure there’s the detailed chemical reaction when you’re browning something, but browning is not the entire thing,” he said. “There are some structural issues, and taste is something that is much more complicated than just a chemical that touches a receptor—there’s a texture, there’s a look.”

Since there is limited space in the kitchen—and thus limited space in the class—Charbonneau said he hopes he can make the topic more accessible to the Duke community through de Valicourt’s office hours and a final banquet.

“The students from the class will help with the cooking and serving of the banquet,” he said. “It’s the chef’s job to be able to teach them (how to cook properly) and to supervise them, so that should be fun. Hopefully we’ll be able to reach as many people as possible.  We got amazing support from everybody in the administration that we talked to. I’m very grateful.”

Since bringing together a chef, a chemist and class space took a “special alignment of the planets to make it happen,” the class—which is being taught for the first time in the spring—may also be its only run.

“The chef is here for a semester, and I would never have dared—because I’m a theorist—to do a thing like this without her or the TA’s,” Charbonneau said. “I do hope though that some of the material we’ve built up will be able to be used as a special topic in general chemistry. I would like to have a module where I would be able to reuse the demonstrations and the content, and maybe even bring in a local chef at that point who would be interested. That’s one way to project it in the future.”

For those interested, the course is called Chemistry and Physics of Cooking, listed as Chem 89.

“It’s listed under chemistry, but it’s really about chemistry and physics,” Charbonneau said. “We’re looking at more physical chemistry—physics processes, denaturing of proteins. We’re also looking at the material science idea, such as viscosity, elasticity—viscoelastic moments, which chemists would never talk about… in a general chemistry class.”

Even ferns get Gaga

by Ashley Mooney

Biology professor Kathleen Pryer discussed the sex lives of ferns with a group of students Monday in the Center for LGBT Life.

“We’re trying to develop a new lifecycle (of ferns) that we hope textbooks will pick up,” Pryer said. “There are a range of ways that ferns have sex and each of these has is own evolutionary consequences and genetic outcomes.”

At the lunchtime lecture, Pryer also revealed her lab’s newly discovered fern species, Gaga germanotta, named after pop star Lady Gaga.

By naming a species after somebody outside of the world of scientific research, Pryer said she wanted to give Lady Gaga a namesake that will recall her activism efforts.

“The work that she’s done, the money that she’s put behind the Born This Way foundation, I think is incredible,” Pryer said. “She’s a real champion for justice and equality, and I wanted to do this so that she would have a scientific namesake—something that will last forever long after she’s gone.”

Lady Gaga also bears some likeness to a fern gametophyte, which is a fern early in its developmental cycle. At the 2010 Grammys, Lady Gaga wore a costume that strongly resembles a gametophyte, Pryer said.

The new species is part of a genus containing 19 species that were originally listed as cheilanthes. True cheilanthes—ones that have kept their original designation—are South American ferns that are nearly indistinguishable from Gaga ferns in appearance. Their differences, she said, are in their DNA.

“When we line up all our sequence data [of the Gaga ferns]… in a particular gene there is a string of GAGA,” she said. “The closest relatives of the genus Gaga doesn’t have that synapomorphy.”

Flowering plants—the most diverse types of plants on the planet with approximately 350,000 species—reproduce using seeds. Ferns on the other hand reproduce through spores contained on the undersides of their leaves.

Pryer noted that many people do not understand the vast diversity of ferns. There are about 12,000 species, including the typical forest ferns, aquatic ferns, desert ones and ferns that are the size of trees.  Pryer’s main focus has been on desert ferns—most of which appear similar but have different DNA patterns.

Beyond the variation in appearance of fern species, Pryer said the plants have multiple mating strategies, even though textbooks usually only teach one form.

Pryer describing the fern lifecycle often depicted in textbooks. Credit: Ashley Mooney.

One of the lifecycles they’re investivating involves a bisexual gametophyte, which is usually the first gametophyte in a population to mature. It forms a notch where it produces archegonia while antheridia develop on the outside. Most ferns have archegonium—the female component where eggs are located—and antheridia, which contain sperm. The gametophyte emits a pheromone that signals to all nearby developing gametophytes that they should become male.

Pryer said the diversity she found in ferns is only one type of sexual diversity in the world, and she hopes that a common interest in such differences will connect her field with the general population.

“We live in this world and we’re all interested in diversity in many different ways,” she said. “This makes a connection between what [scientists] do and human diversity and it also makes people who are Gaga fans say, ‘hey, what’s up with these botanists.’ I’m hoping that we can engage the two communities. When people talk about interdisciplinary work, I’m taking it to ‘the edge of glory.’”

YouTube Video about the naming: 19 Species of Ferns Named for Lady Gaga

Duke Today coverage: http://today.duke.edu/2012/10/gagafern

 

A "Neurodiverse" View of Poetry

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.”

Football Player Makes an Impact

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

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

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.

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