Student Cameron Kim, Working to Reprogram Cells

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.

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.

Biomedical Engineering Seniors Share Novel Research

By Nonie Arora

Pratt senior Alex Sun hopes to be able to repair cartilage using stem cells.

Alex Sun at BME Reception

The study Sun has been working on in Dr. Farshid Guilak’s laboratory has found that engineered cartilage constructed from a particular type of stem cell integrate well with host cartilage, but not necessarily in a uniform way.

Sun was one of about thirty biomedical engineering students who presented at the department’s graduation with distinction reception on April 26. Other students have been working on exciting projects in optic imaging of tumors, synthetic biology, and deep brain stimulation, among other topics.

Sun’s project focused on how induced pluripotent stem cells can be used to study cartilage regeneration and repair.

Sun said articular cartilage has limited healing potential and contributes to progressively degenerative diseases like osteoarthritis. The best treatments now require major surgery and total joint replacement. But spontaneous cartilage healing does happen in some animals, like fetal lambs and infantile rats. Better understanding these mechanisms for spontaneous repair could allow for their eventual integration into therapy.

Students Converse at BME Graduation with Distinction Reception

Like many of the seniors graduating from BME with distinction, Sun’s research career has just begun. After graduation, he will be headed to the Netherlands to work on a tissue engineering project sponsored by the Whitaker International Fellowship. 

Probing our Internal Universe

By Prachiti Dalvi

Dr. Nicolelis was recently featured on the Daily Show with Jon Stewart to discuss his new book: Beyond Boundaries.

At the 2014 FIFA World Cup, Dr. Miguel Nicolelis hopes to see a quadriplegic child walk into the pitch and deliver the kickoff of the opening game. A pioneer in brain machine interface research and recent author of Beyond Boundaries, Nicolelis gave an evening talk on March 14 at the Nasher as a part of Brain Awareness Week.  Dr. Nicolelis grew up in São Paulo and came to Duke in 1993. Since then, he has focused his research efforts on facilitating two-way dialogue between brains and machines.

Recent advancements in biomedical engineering allow us to use filaments implanted in several parts of the brain to obtain brain function readings: something that was impossible several decades ago. In one of Dr. Nicolelis’s first experiments, monkeys learned to use a joystick to catch a moving object on a screen. After the monkey was able to accurately catch the object 90% of the time, a brain-machine interface was turned on linking the robotic arm to the brain signals. The joystick was eliminated from the setup. The only way to obtain the reward (Brazilian orange juice) was to imagine catching the object.

The brain-machine interface allows for the translation of mental movements into digital commands while recording muscle activity. Using data collected from this experiment, on March 28, 2003, the Nicolelis team was able to design and operate the first robotic arm.

Until recently, neurons were considered the basic functional unit of the brain. More recently, scientists have focused their attention on populations of neurons as functional units instead.

Nicolelis and others are focusing on cell assembles as key functioning units of the brain, not simply neurons. “Populations of neurons across multiple brain structures are working together to make movement possible,” says Nicolelis. Thus, a holistic approach of looking at brain activation is necessary to understand and replicate movement in machines. Differences in the number of neurons activated have been observed when neurons are operating a robotic arm instead of a biological arm.

In a second set of studies, Nicolelis studied the effect of virtual simulations on the brain’s ability to assimilate other things as extensions of the human body. For example, if a professional tennis player is blindfolded and asked to point where his/her arm ends quickly after they have been playing tennis for an hour or so, they will point to the end of the racket as the end of the arm. In other words, the tennis player is assimilating the racket as an extension of the body. Similarly, if a monkey sees a knife approaching a rubber limb that is in the place where his arm should be, he will experience the anxiety, increase in heart rate, and even remove his real arm away from the perceived source of danger.

In an international collaboration with a team from Kyoto, Japan, researchers were able to send brain activity data of a monkey walking on a treadmill to a robot in Japan. The video of the robot walking was then transmitted back to the monkey. Even when the treadmill was stopped, and the monkey was rewarded for each step the robot took, the monkey began imagining that she was the one taking steps in order to be rewarded.

This brain-machine interface research has interesting implications in medicine, ranging from spinal lesions to Parkinson’s disease. When a spinal lesion forms, the brain continues to produce brainstorms to direct movement; however, the body does not have access to muscles. This is where the brain-machine interface comes into play: the brain can provide the directions that can be converted to digital commands, which can ultimately lead to functioning of the machine. To use the brain-machine interface to treat Parkinson’s, Dr. Nicolelis has been using a mouse model developed by Dr. Marc Caron in which 80% of the neurotransmitter dopamine is depleted. The rigid movements of Parkinson’s patients can be refined using brain-machine interface technology.

The brain-machine interface has the ability to alter medicine tremendously.

Dr. Nicolelis’s research implies that it is “possible to use brain activity beyond epithelial boundaries we have,” he says. Perhaps we will be able to do things using this technology, which we customarily cannot do because of the physical constraints of our body because there is no limit to what our minds are capable of doing. “There is a tremendous range of opportunities in this field.”

With the progress the Nicolelis lab is making, perhaps we will be able to see something truly unique at the 2014 FIFA World Cup in Brazil!

 

 

Catching the Space Bug

Prachiti Dalvi

Robert Satcher, MD, PhD –the first orthopedic oncologist to orbit the Earth –discussed his interest in telemedicine and telesurgery during a school of medicine seminar last month.

Growing up not to far from Duke in Denmark, South Carolina, Dr. Satcher developed a profound interest in science and chose to pursue chemical engineering at MIT. After graduating at the top of his class, he entered the MD/PhD program just across the river at Harvard Medical School and returned to MIT to complete his PhD in chemical engineering.

Then, he followed the more conventional route of interning in general surgery and spending his time as a resident at UCLA. Deciding to further specialize, Dr. Satcher proceeded with an orthopedic oncology fellowship at the University of Florida. For a short time period, Dr. Satcher was an assistant professor at Northwestern before he caught the space bug. Satcher successfully completed a rigorous application and interview process and was elected to begin space training at NASA.

Although his interests span chemical engineering and orthopedic oncology, he is particularly interested in bone mineralization, nanomaterials, and bone metastasis in cancer. At the MD Anderson Cancer Center he is exploring telesurgery and telemedicine. In November 2009, Dr. Satcher went into space as a mission specialist on Atlantis, spending more than 200 hours in space and engaging in more than twelve hours of spacewalk.

“Medical knowledge comes into play when people are going through adaptation in aerospace,” Satcher said. While in space, Satcher performed maintenance and conducted research on how the human body reacts in space. His own research interests resonated through when he was able to study how bone density and skeletal muscles are affected by zero gravity. Dr. Satcher likened walking in space while inspecting the station’s outside equipment to surgery: attention to precision is vital. To complete this task, he was able to use his surgical skills to navigate a robotic arm to scan the shuttle for damage.

Although space exploration comes with some dangers and difficulties, Satcher believes space exploration is important because there is a lot we still do not know. According to Dr. Robert Satcher, the common thread of curiosity for the unknown ties space exploration and medicine.

Detecting disease with sound

By Becca Bayham

Most people experience ultrasound technology either as a pregnant woman or a fetus. Ultrasound is also employed for cardiac imaging and for guiding semi-invasive surgeries, largely because of its ability to produce real-time images. And Kathy Nightingale, associate professor of biomedical engineering, is pushing the technology even further.

“We use high-frequency sound (higher than audible range) to send out echoes. Then we analyze the received echoes to create a picture,” Nightingale said at a Chautauqua Series lecture last Tuesday.

According to Nightingale, ultrasound maps differences in the acoustic properties of tissue. Muscles, blood vessels and fatty tissue have different densities and sound passes through them at different speeds. As a result, they show up as different colors on the ultrasound. Blood is more difficult to image, but researchers have found an interesting way around that problem.

“The signal from blood is really weak compared to the signal coming from tissue. But what you can do is inject microbubbles, and that makes the signal brighter,” Nightingale said.

Microbubbles are small enough to travel freely throughout the circulatory system — anywhere blood flows. Because fast-growing tumors require a large blood supply, microbubbles can be particularly helpful for disease detection.

Like most other electronics, ultrasound scanners have gotten smaller and smaller over the years. Hand-held ultrasounds “are not as fully capable as one of those larger scanners, just as with an iPad you don’t have as many options as your computer or laptop,” Nightingale said. However, the devices’ portability has earned them a place both on the battlefield and in the emergency room.

Nightingale’s research explores another aspect of ultrasonic sound — its ability to “push” on tissue at a microscopic scale. The amount of movement reveals how stiff a tissue is (which, in turn, can indicate whether tissue is healthy or not). It’s the same concept as breast, prostate and lymph node exams, but allows analysis of interior organs too.

“We can use an imaging system to identify regions in organs that are stiffer than surrounding tissue,” Nightingale said. “That would allow doctors to look at regions of pathology (cancer or scarring) rather than having to do a biopsy or cut someone open to look at something.”

Mapping Movement

Guest Post By Viviane Callier

The way your brain tells your hands and feet to move is unique to you.  Your brain uses a map to control where your hands are going, and your map wouldn’t work in anyone else’s head.  Understanding how these maps are created in different brains, and how unique they are to individuals, is key to designing next-generation prosthetics.

You have a map in your head that coordinates physical movement. It wouldn't work in any other head, or body.

In contrast to a robot, the brain is not programmed to solve mathematical equations for the forces required to produce a given movement.  Instead, it learns both forward maps, which link a firing pattern of neurons to a specific movement, and inverse maps, which are used to infer the pattern of neuron activation pattern required to produce a desired movement. These maps are built through trial and error, and kept in memory. Due to the randomness involved in trial and error exploration, no two brains build quite the same movement maps.

To study the process by which brains learn these maps,  Tim Hanson, a graduate student in the neurobiology lab of Miguel Nicolelis, has been using electrodes to record activity patterns from individual neurons in the brains of monkeys who are learning to control prosthetic arms.

The team wants to design a general way to connect prosthetics to a person’s individual brain map, which is a challenge because no two brains make the same map.  The commonality between people is not the particular maps, but rather how these maps are learned.  Therefore, future brain-controlled prosthetics need to integrate well with the biological process by which these maps are learned.

By recording the activity of the brain and correlating it with behavior over time as control of the prosthetic arm improves, Hanson can visualize the map being created in the monkey’s brain.

Observing the learning process in real time in a monkey’s brain will further understanding of how we learn, and potentially aid prosthetic design, Hanson says.