Doctoral Students Without Borders

To train scientists of the future, Pitt rethinks what a graduate program in the life sciences should be

In the past generation or so, scientists have been rethinking how they study human biology. Today’s powerful imaging helps them see how a cell’s tiniest particles behave. The untangling of the human genome allows them to trace precisely how human bodies are built, or impacted by disease. Scientists borrow techniques from disparate disciplines to sort through the big questions of biology: Why do cancer cells behave the way they do? How does the brain work? Can we rebuild dead tissue? They use molecular biophysics, pharmacology, and cognitive psychology to study mental illness; they use mathematics, computer science, and chemistry to study cancer.

Clearly, this is a brave new world. It’s also a challenging landscape to train the next generation of researchers in the biomedical and biological sciences. After all, the disciplines may look entirely different in 20 years. But the University of Pittsburgh has emerged as a leader in training young scientists in this new terrain—mainly by rethinking the very notion of what graduate studies can be.

It has established new graduate programs that are based upon collaborations among schools within the University, including the schools of medicine, arts and sciences, and engineering.

“We’ve consciously tried to develop this approach,” explains Provost James V. Maher. “Creating these programs has gone hand in hand with strides in biological and biomedical research at Pitt. The old distinctions between disciplines are increasingly becoming obsolete. Scientists need to be able to think across traditional boundaries to solve the big questions. We find it is these PhD programs we are creating—and the students themselves—that are breaking down walls, unifying both the research and graduate study across this campus and beyond.”

This wave of innovation began in the 1990s, with the creation of programs in neuroscience and bioengineering. More recently, we developed PhD programs in computational biology, molecular biophysics and structural biology, and integrative molecular biology to capture trends in emerging fields. “Many of these fields simply didn’t exist a generation ago,” says Maher. “We created these programs to stay ahead of the curve in training the professors and researchers who will shape the next generation of science. We’re training people to address the questions of the future even though we often don’t know what those questions will be.”

Arthur Levine, senior vice chancellor for the health sciences and dean of the School of Medicine, says the programs leverage Pitt’s considerable research talent in the biological and biomedical fields. The University of Pittsburgh faculty ranks 6th in the nation in grants from the National Institutes of Health (NIH)—the gold standard for measuring a university’s biological and biomedical research prowess.

“I think the interdisciplinary nature of these programs reflects the science of the times in which we live,” says Levine. “There are excellent investigators across this campus and at Carnegie Mellon, and we need to take advantage of that.

“It makes a lot of sense to bridge disciplines, to bridge ideas, and to use different technologies. It’s where the science is leading us. There have been so many changes in technology over the last 20 years. We now have tremendous database resources, very sophisticated imaging, and new ways of tracking molecules within single cells. We’ve learned more about the biology of the human body in the last 20 years than in the history of science,” Levine adds.

The structural biology and molecular biophysics program was created in 2005 to train students in a field that emerged from breakthrough imaging technology that allows scientists to “see” the smallest parts of the human cell. In the computational biology program, students use mathematics and computer science to model complex biological phenomena. The integrative molecular biology program trains students in a broad array of research topics, such as genomics, proteomics (the study of the body’s proteins), gene function, and cell and developmental dynamics.

N. John Cooper, the Bettye J. and Ralph E. Bailey Dean of the School of Arts and Sciences, says the interdisciplinary programs have enabled the school to recruit top-flight faculty and graduate students.

“To be cutting edge, you have to provide the opportunity for faculty and graduate students to get in-depth in these interdisciplinary areas. You need to be ahead of the curve in creating these programs. I think that Pitt, in the last five years, has been moving faster than other places. And we are now thinking about the next generation,” he says.

One such key recruitment was the School of Medicine’s hiring of faculty member Angela Gronenborn, UPMC Rosalind Franklin Professor and chair of the Department of Structural Biology. Gronenborn came to Pitt from the National Institutes of Health, where she developed and used nuclear magnetic resonance to study cellular processes at molecular and atomic levels.

She says her field involves an interaction between disciplines that was rare 30 years ago. “A physicist never used to talk with a biologist during their studies,” says Gronenborn, who was elected to the National Academy of Sciences in 2007. “Students should move seamlessly across those boundaries. In terms of their education, and of science in general, those boundaries to me are artificial.”

NEUROSCIENCE

One of the earliest and best examples of these interdisciplinary and inter-school graduate programs is neuroscience. Through the Center for Neuroscience at the University of Pittsburgh (CNUP), PhD students have access to more than 90 faculty in more than a dozen departments across the campus and beyond.

“What I like about it is we encompass a huge neuroscience community,” says Beth Siegler Retchless, a PhD candidate. Siegler Retchless majored in neuroscience as an undergraduate at Brown University. When choosing a graduate school, her adviser cited Pitt as one of the top neuroscience programs in the country. “We have people from all over the University—and the University is huge. All these people work on different aspects of brain function—everything from MRI studies, where they can look at what areas of the brain are active during a learning task, to figuring out how molecules work, and everything in between.”

Siegler Retchless is conducting her doctoral research on a protein that acts as a target for glutamate, a neurotransmitter important for learning and memory. She studies how a single amino acid can change the behavior of the protein, which is found in brain cell membranes. When activated by glutamate, the protein opens up a pore in the membrane through which electricity can flow. But sometimes the pore is blocked by specific ions—and Siegler Retchless wants to know why. Scientists believe that learning more about these targets will give insight into how complex phenomena like Alzheimer’s and schizophrenia work. Siegler Retchless says she has relied on mentoring from CNUP faculty in an array of disciplines—mathematics, molecular genetics and biochemistry, and neurobiology.

“The degree of collaboration here means I have this tremendous resource that just isn’t available in other places,” she says.

Alan Sved, CNUP codirector, professor of neuroscience, and chair of that department, says the program is designed to give students a broad range of experiences and skills as they begin their scientific careers. “We’re not simply a collection of outstanding neuroscientists. We’re an interactive group of outstanding neuroscientists. Students aren’t simply working with one primary investigator locked away in a lab somewhere.”

It wasn’t always this way. For years, Pitt neuroscientists were scattered around the campus—some in neuroscience within the School of Arts and Sciences, some in neurobiology within in the School of Medicine. This worked well enough, but it confused many within and outside the University. What’s the difference between neuroscience and neurobiology? In truth, there wasn’t much of one, says Cooper.

So Pitt united these programs under the CNUP banner—bringing together psychologists, cell biologists, pathologists, and others for research and graduate training. “The idea was that instead of running two PhD programs that would be different, but look similar and confuse everybody, we should combine the resources into a single PhD program clearly focused on neuroscience. It provides a well-marked, come-in-the-front door approach,” Cooper says.

Creating the CNUP graduate training program gave Pitt one of the top-ranked neuroscience programs in the country. Incoming students’ average GRE and GPA scores are well above the national average for other neuroscience programs. Most of the students are drawn by their intense interest in research. They have the opportunity to work in a number of CNUP-affiliated research groups—such as those focused on aging, Alzheimer’s disease, Parkinson’s disease, schizophrenia, and pain.

But the integration didn’t just happen. The University worked hard to break down traditional barriers between disciplines, Sved says. For instance, there was a learning curve before students in Arts and Sciences and the medical school faculty became accustomed to working with one another—and vice versa.

“It was a major divide,” Sved says. “It was a barrier to doing things. Now, we don’t even see it. It is transparent to the students. We have students who on any given day couldn’t tell whether they were working with Pat Card, (professor in Arts and Sciences’ neuroscience department) or Bill Yates (professor in the School of Medicine’s otolaryngology department). In fact, they’re working with both of them.”

David Moorman, who received his PhD in neuroscience in 2005, did his doctoral research at the CNUP and the Center for the Neural Basis of Cognition, a joint Pitt-Carnegie Mellon University initiative. He worked with neuroscientists, computer scientists, and psychologists to study the way the brain processes certain kinds of spatial information. Each faculty member brought different skills and strategies from their discipline, their own particular “toolbox.”

“Part of it just has to do with knowing what techniques are available to you,” says Moorman, now a postdoctoral neuroscience fellow at the Medical University of South Carolina studying the neural basis of drug addiction. “If your research lies at the interface of all these different disciplines, you have to pay attention to all these different things.”

At Pitt, he studied cognitive neuroscience, which is the study of neural circuitry underpinning cognition and behavior. In his current fellowship, he’s had to learn a more molecular approach to neuroscience—studying drug targets on specific neurons. The CNUP’s emphasis on collaboration laid the foundation for Moorman to learn from others in his current lab.

“It’s almost impossible to use all these techniques yourself. If you want to ultimately tackle some of these problems, you’re going to have to work with other people. That’s how the big problems get solved,” Moorman adds.

Susan G. Amara, CNUP codirector, Thomas Detre Professor, and chair of the Department of Neurobiology, says graduate students need to be able to keep pace with the rapidly changing field.
“One of the interesting challenges for neuroscience education is training students to be adaptable, to be nimble when they’re confronted with the landscape of the future,” says Amara, a member of the National Academy of Sciences. “The important thing we do here is create a mindset of problem-solving, rather than a specific technique that you master. We can train students for what they do now, but they’re not going to be doing what they do now forever.”

BIOENGINEERING

Pitt’s Department of Bioengineeering has a long history of training students to use multiple disciplines to tackle complex medical and biological problems. The department celebrated its 10th anniversary last fall, but its roots go deeper. Pitt bioengineers were instrumental in UPMC’s groundbreaking artificial heart program, which implanted its first artificial heart device in 1985, and discharged the first patient on a ventricular-assist device five years later.

Today, Pitt’s bioengineering program is among the best in the country, ranked in the top 10 by such publications as U.S. News & World Report.

“Our students come from everywhere, they’re interested in everything,” says Harvey S. Borovetz, chair of the Department of Bioengineering and Robert L. Hardesty Professor of Surgery. “Every year they become more and more diverse.”

Though their degrees are granted by the Swanson School of Engineering, graduate students conduct research in labs at the School of Medicine, the McGowan Institute for Regenerative Medicine, the University of Pittsburgh Cancer Institute, the School of Dental Medicine, the Graduate School of Public Health, and the School of Health and Rehabilitation Sciences, in addition to laboratories within the Swanson School.

This open access to broad swaths of campus expertise, Borovetz says, “is not part of the reason for our success. It is the reason. It’s what other places would love to be able to claim.”

From his office in Benedum Hall, Borovetz has a view of the medical school and UPMC’s training hospitals perched atop “Cardiac Hill.” It is a reassuring sight for Borovetz, who spent two decades in Pitt’s artificial heart program, along with cardiac transplant surgeons and cardiovascular physicians at UPMC and the School of Medicine.

The bioengineering program’s success stems in large part from its access to clinical settings, lab space, and faculty talent provided through its unique partnership with the medical school. “We are totally integrated with the School of Medicine,” says Borovetz. “That gives our students opportunities that are, quite frankly, limitless in terms of what they want to do.”

Rebecca Long, a fifth-year PhD student, uses the science of mechanical engineering and physiology to conduct basic research into tissue engineering science. With biomechanics, Long says, “you’re taking principles you learn in mechanical engineering or basic physics and seeing how to apply them to things that don’t behave like a steel beam. It’s taking those same concepts and using them to learn how the body works.”

Long, who majored in chemical engineering and biomedical engineering at Carnegie Mellon as an undergrad, was drawn to Pitt’s program by the opportunity to work with Michael S. Sacks, William Kepler Whiteford Professor of Bioengineering. In 2006, Sacks shared a Scientific American 50 award with William R. Wagner, deputy director of the McGowan Institute and a professor of surgery, bioengineering, and chemical engineering. The award recognized their pioneering research into tissue engineering.

For her PhD dissertation, Long is studying the biomechanics of bladder cells. Sacks, Wagner, and their McGowan Institute colleagues are working to engineer soft tissue that could eventually replace defective tissues, such as heart valves. Long’s research on cell behavior in the bladder—an organ which frequently atrophies following a spinal cord injury, could lead to drugs to prevent urinary tract problems in spinal patients.

Pitt’s bioengineering program prepared Tim Maul (ENGR ’07) well for the inter-disciplinary environment of biomedical research. A postdoctoral fellow in Wagner’s lab at the McGowan Institute, Maul is working to design injectable polymer- and lipid-based microbubbles that will seek out inflamed blood vessels. His current lab includes a biophysicist, a biochemist, a physician, and a chemical engineer. “The bioengineering program is the ideal incubator for learning how to grow in this kind of environment,” he says. “Working in these highly interdisciplinary teams is the key to having big successes in research.”

For his doctoral research, Maul studied the mechanics of stem cells—how they reacted to conditions similar to those inside a blood vessel. His work touched several different disciplines—mechanical engineering, cellular and molecular biology, and statistics. He worked with chemical and molecular biologists, and experts in tissue engineering. “A lot of times, people who study biology and mechanical engineering or chemical engineering have a hard time communicating because they don’t speak the same language. But I learned in my labs how to learn from people around me.”

Students coming out of the program enter a field bursting with opportunities in private industry, academia, and government-funded research institutions. Borovetz is convinced that Pitt is training the next generation of leaders in fields such as tissue engineering, imaging technology, and prosthetics.

“I don’t know how or when, but I know that this is going to be the place where you’re going to see these kinds of discoveries being made. That’s what’s so great about having our students participate in this research. Turn them loose and they’re going to bioengineer great solutions down the road,” Borovetz says.