Research Magazine 2009

Research Realized

Research doesn’t happen overnight. There are often years of preparation leading up to each eureka moment. Usually a similarly unglamorous period of work is needed afterwards to turn bright ideas into thought-provoking books and promising discoveries into useful, usable products.

BU is committed to supporting the research process from beginning to end: encouraging students to take an early interest and initiative in pursuing original research through the Undergraduate Research Opportunities Program; fostering corporate and government partnerships in order to test ideas in real-life contexts quickly and effectively; and supporting faculty through the technology development and transfer process.

All with one goal in mind: to make sure that BU researchers are making an impact.

Inspiration + Perspiration = Commercialization

illustration of polyclonal and monoclonal antibodies

Antibodies are used by the immune system to identify and help rid the body of foreign or abnormal entities, such as microbes and cancer cells. Above left: A polyclonal antibody creates a much denser target coating than does a monoclonal antibody. The denser target coating sends a stronger signal to effector cells, which then destroy and dispose of the target. Above right: Scheme for generating a recombinant polyclonal antibody.

Illustration by Anna Belkina

Known as the “silent thief,” osteoporosis affects an estimated 12 million Americans over age 50 and threatens another 48 million who are at high risk for developing it. Individuals with this bone disease can break a leg merely by stepping off a curb, or break an arm while putting on a seat belt.

Nathan Wiger

A postdoctoral research fellow in the School of Medicine, Nathan Wigner is investigating new therapeutic approaches to reverse the effects of osteoporosis, thanks to an Ignition Award from BU’s Office of Technology Development. In the process, he is also learning how to align the business side of new technology with the science, in order to turn a promising discovery into a tangible product that can help those suffering from bone loss.

Catherine Klapperich

With a $2.9 million Translational Partnership Award from the Coulter Foundation, Assistant Professor of Biomedical Engineering Catherine Klapperich created a small, inexpensive device that uses microfluidic action to extract nucleic acids from saliva, blood, and other bodily fluids to isolate biomolecules. Her “lab on a chip” could someday enable point-of-care flu diagnostics that would significantly reduce the spread of infection.

Jacqueline Sharon

Immunologist Jacqueline Sharon has always had an interest in translational research, but after two patents she realized that her lab alone would be hard-pressed to take on the development of a new class of therapeutic polyclonal antibodies. So she licensed the technology to Symphogen, a biotech company that is now in clinical trials for two drugs based on her ideas.

David Rosenbloom

Early on, Professor of Social and Behavioral Sciences David Rosenbloom saw how the Internet could be used to make effective strategies for fighting substance abuse quickly and widely available. To date, his QuitNet website—which was incorporated in 2000 with support from BU’s Community Technology Fund—has helped more than a million people stop smoking, saving them over $2.7 billion and 224,000 years of life.

Bennett Goldberg and M. Selim Ünlü

The Numerical Aperture Increasing Lens technique developed by Bennett Goldberg, right, and M. Selim Ünlü has demonstrated a five-fold improvement over current optical technology. This high-resolution subsurface imaging technique was licensed to Hamamatsu, a Japanese company that manufactures imaging and analysis tools for semiconductors. The quicker and more precisely Hamamatsu can detect potential defects and design errors in their semiconductors, the better, in an industry where each minute’s delay can cost tens of thousands of dollars.

Nathan Wigner, a postdoctoral research fellow at BU’s School of Medicine, is working to find a better drug to combat osteoporosis. He is coming at it from an unusual and slightly counterintuitive angle, focusing on the bone-restoring properties of anthrax receptors in the skeleton. “I almost wish it had a different name,” he says, both because it can be confusing when people learn that what Wigner is working on has nothing to do with anthrax toxicity and, he jokes, because “I’m sure my name is on some sort of governmental registry for Googling ‘anthrax’ as many times as I have.”

The link between osteoporosis and anthrax receptors, though unlikely, holds promise. But even after initial in vitro studies confirmed that these receptors are molecular targets capable of restoring bone mass, Wigner knew that potential applications could be months or even years away, if they materialize at all, and that funding is often scarce for projects at this critical interim stage.

So he applied for an Ignition Award from BU’s Office of Technology Development (OTD), and won. Now, says Wigner, his lab has “the resources to see this technology through the next phase of development—to demonstrate the in vivo therapeutic potential of targeting these receptors in osteoporotic mice. And without something like the Ignition Award, it just wouldn’t happen.”

Ignition Awards—which are designed to help bring raw technology and business concepts to a mature enough stage where they can be licensed or used to form the basis of a new company or nonprofit social enterprise—are just one of the many supports available to BU researchers through OTD.

Because the process of translating scientific discoveries into tangible products can be “complex and sometimes intimidating,” says Michael Pratt, director of translational research and corporate relations, he and his colleagues “are pursuing a University-wide approach and working to support the translational process at every phase of development—from the formation of collaborative teams, to funding and guiding translational research projects toward appropriate endpoints, to identifying industry collaborators and mentors to support new company development.”

Additional features of their work include support for patent filings, licensing, market research, start-up development, and business incubation. OTD also collaborates with various research programs, including the Center for Integration of Medicine & Innovative Technology (CIMIT) and the Wallace H. Coulter Foundation, to support the translational research process and to promote collaborations between biomedical engineers and clinicians. In a typical year at BU there are as many as 100 new technology disclosures, scores of U.S. patent filings, and a dozen exclusive licenses.

Among the many success stories is Jacqueline Sharon’s. In the 1990s, Sharon, a professor of pathology and laboratory medicine, and her colleagues developed a novel method of cloning antibodies.

“As an immunologist,” she says, “I recognized that the polyclonal antibodies that our body produces are much better than the monoclonal antibodies” that are the basis for many medications. She theorized that recombinant—that is, industrially refined and standardized—polyclonal antibodies could be constructed which would mimic and expand the natural antibodies found in survivors of particular diseases. More effective manufactured antibodies might then be bottled and prescribed for those illnesses, Sharon predicted.

Her lab began developing a process for creating cells expressing recombinant polyclonal antibodies, and earned two patents on their work before deciding that the amount of money and effort needed to see the technology through to market was overwhelmingly prohibitive.

In 2000, Boston University licensed the technology to Symphogen. At the time, the Danish company had only three scientists, who initially shared Sharon’s lab space at BU, and three executives, who flew back and forth from Denmark. Today, Symphogen is a rising star of biotech, employing 70 people in Copenhagen, who are developing recombinant human polyclonal antibodies against several infectious disease and cancer targets as well as human cells associated with certain immunologic diseases. The company’s most advanced product, currently in Phase 2 clinical trials, is a drug that would treat idiopathic thrombocytopenic purpura and prevent hemolytic disease of the newborn, two immunologic diseases which involve uncommon susceptibility to bleeding.

“They’ve done a wonderful job of developing and marketing the technology and really doing production—things that my lab is neither qualified to do nor interested in doing,” says Sharon, who served on the company’s scientific advisory board. “That’s the great value to the technology transfer process. I enjoy being in academia, with the freedom to pursue research at the basic science end. But it’s been very satisfying to watch Symphogen, and rewarding to see what we started many years ago turn into something applied that ideally will be able to help people very soon.”

That is also what Wigner eventually hopes to achieve with his research on osteoporosis. If his team’s in vivo research goes well, the result may be a therapeutic that will not only stop bone loss but reverse it. This would be a tremendous improvement over current treatment options, which can slow bone loss, but not prevent it completely or restore lost bone. Over time, the condition “steals more than just bone,” Wigner says. “Out of fear, you’ve become that grandparent sitting alone on the beach just ‘minding everyone’s shoes’ instead of playing in the sand with your family.”

That’s how he described the plight of individuals with osteoporosis in his project proposal. “I was thinking about my mom,” he explains, “because she used to say, ‘I’ll just sit here and watch the shoes,’ and there may be a point when that’s all she can do.”

Wigner chose not to keep emotion out of his pitch because despite being a “straight science head,” he has learned over the past year that presentation counts. “If you truly believe in your science and you believe in your idea, and you’re willing to take some risks and put extra effort into it, business-minded people pick up on that really quickly.”

Pratt and the Technology Development staff, Wigner says, have helped him understand how to align the science side of a project with the business side, in order to keep it moving forward. “They’ve been phenomenal. I’ve never met a group of people who are so willing to sit—and yes, it’s their job, but it’s not their job to do it with a smile and be excited to talk to me about the science—to sit and really plan how to carry this out.”

Charting a New Geography of Work

N. Venkat Venatraman

N. Venkat Venatraman

Photo by Len Rubenstein

The changing nature of work in the 21st century requires more than a fast Internet connection, an extra clock set to Jakarta time, and a functional knowledge of outsourcing. It calls for nothing less than a paradigm shift in the way businesses view the world, and the strengths and desires of its occupants, says N. Venkat Venkatraman, the David J. McGrath, Jr. Professor of Management, Strategy and Innovation in the School of Management.

Globalization 3.0 is an era in which “hugely powerful computers and communication technologies are available worldwide at a relatively low cost,” he explains, which means that anyone who visits an Internet café in Andalusia or Angkor Wat can now imagine life as an actor, CEO, or high court judge. The unprecedented scale of this global talent pool presents significant opportunities for companies—but only if they know how to navigate what Venkatraman calls the “new geography of work.”

The complexity of tapping into global talent pools is just one example of how new contexts demand new best practices. Identifying and articulating these best practices—by assessing how well multinational companies are making the transition to truly leveraging global talent and expertise, and by generating new ideas which are then swiftly applied in the workplace via partnerships with government, academe, and industry—is the goal of BU’s Institute for Global Work.

Launched in 2007 with a nearly $1.7 million grant from the Keane Institute, the institute is led by director John Henderson and education director Kathleen Curley, both professors in the Department of Information Systems. Drawing on the vision and expertise of colleagues such as Venkatraman, they are driving research and thought leadership that will shape the next generation of global business processes.

Already, the Institute for Global Work has formed partnerships with a number of businesses and universities at home and abroad. So far these include American companies Thermo Fisher Scientific, John Hancock, and Parametric Technology Corporation, as well as Switzerland’s University of St. Gallen, Israel’s Ben-Gurion University, and Mexico’s Monterrey Institute of Technology and Higher Education.

“We’re looking at similar kinds of questions, so the idea is to share results,” says Curley. “What is the future of work going to look like? How are people going to do it? Different markets and different contexts give people insights into different possibilities.”

For example, she says, “A lot of Israeli companies are smaller, but they’re very quick and they’re big on exporting and reaching other markets. What they bring to the table is this ability to test something in a demanding market at home and then quickly try it on the European market.”

In Mexico, meanwhile, the emphasis is on keeping costs low, which could offer valuable insights for entrepreneurs interested in developing better water purification systems or other technologies for which there is a high demand in developing countries. “If you’re going to be successful in emerging economies,” Curley says, “you’re going to have to figure out how to do it on the cheap.”

In January 2009, the Institute for Global Work offered its first course for executives, a three-day seminar entitled “Making Global Work Work.” The well-received program, which was partially funded by the U.S. Department of Labor, was repeated in July and will be offered on a quarterly basis. A separate conference on global business practices is in the works.

The institute’s international collaborations are also giving graduate students in the BU School of Management an edge. By collaborating on business plans with their peers at Ben-Gurion, they are gaining firsthand experience with global virtual teams—that is, teams whose members are spread across different countries and continents—and also increasing our understanding of how such teams function and how they can be most effectively managed.

“The current model is based on our experience with collocated teams,” says Curley. “It turns out that it’s very difficult to replicate that when teams are distributed across multiple time zones.”

The Institute for Global Work is eager to expand this program to the undergraduate level, says Curley, “so that students have this real and practical experience of working with their counterparts in a far-off time zone, and for whom English is not a first language.”

Someday they may take it even further than that. Says Venkatraman, “My ideal would be to get every student at BU—whether in the School of Management or not, and even if they never live or work outside of the United States—to have exposure to their present and future role in the global world.”

Opportunity Awaits:
Undergraduate Research

“You come to UROP to learn—to discover something about yourself and the world,” says computer science major David House. He is one of the more than 500 students over the last decade to be funded through BU’s Undergraduate Research Opportunities Program (UROP). Mentored individually by faculty members who oversee their projects, UROP students expand their academic perspectives by working in a true research environment, and often make their mark by contributing original ideas and discoveries.

With guidance from Margrit Betke, an associate professor of computer science, House is developing a computer program that helps track and model cell behavior by employing computer vision techniques.

These techniques identify and measure cells automatically—without the need for human intervention—and enable computers not only to see, but to understand and predict the behavior of imaged cells. Already, House and Betke have tested this program in the lab, enabling biologists at BU to accurately and expediently track and analyze the migration patterns of cells for the first time.

Betke encouraged House to branch out into other disciplines in order to create a computer program with wide relevance and broad applications. “I knew a bit about computer science, but Professor Betke encouraged me to increase my biology knowledge in my free time in to order to really understand all aspects of the program,” he says. “We wanted to make something that could expedite biological research across the board.”

Associate Professor of Biomedical Engineering Joyce Wong provided an overview of the biomaterial research community’s work in automatically tracking cells, which Betke and House used to design computer programs and algorithms that would model cellular behavior. The algorithms, says House, “can be applied to a variety of biological systems—cells, mammals, anything with heat. We also want to make the computer program open-source, so eventually any college can use it in many different ways.”

“Professor Betke encouraged me to increase my biology knowledge in my free time in order to really understand all aspects of the program. We wanted to make something that could expedite biological research across the board.”

Another UROP participant, biochemistry and molecular biology major Florencia Rago, was named a Beckman Scholar in recognition of her outstanding research in biological sciences.

“As you get to upper-level classes, you have more time for things that are important and interesting to you,” says Rago. In her case, that meant more time in Biology Professor Dean Tolan’s lab, where she is studying aldolase—an enzyme involved in breaking down sugars such as glucose and fructose and converting them to energy—and how it recognizes intermediates in the breakdown process. “The more we see how enzymes are able to sort through everything that’s in a cell that tries to react with them,” she explains, “the more we can understand how it might be possible to develop and manipulate the enzymes.”

That information, in turn, could provide valuable insights for doctors and scientists trying to help people who cannot metabolize certain sugars, or those with metabolic disorders such as hereditary fructose intolerance, a condition that leads to high levels of fructose-1-phosphate, impeding the body’s ability to metabolize fructose and resulting in severe hypoglycemia.

Not all UROP projects require long hours in the lab—some require long hours at the library instead, as Katie French knows well. A double major in classics-religion and archaeology, she is researching the Gospel of John with Assistant Professor of Theology Jennifer Knust, “reading book after book on everything from how codices were produced in antiquity to the role of scribes in shaping the texts they produced.”

video frames of computer algorithms tracking cell movement
computer image of a monomer of aldolase A

Left: Two computer algorithms designed to track the movement of individual cells show suboptimal, top row, and optimal results. The optimal algorithm successfully resolves the track switch for cells 5 and 16 seen in frame 36 of the suboptimal algorithm. Right: a monomer of the enzyme aldolase A, the subject of biochemistry and molecular biology major Florencia Rago’s research.

Video frames courtesy of David House and Margrit Betke

Image of enzyme courtesy of Florencia Rago

In particular, French is investigating the textual history of a well-known passage in John, called the pericope adulterae, where Jesus encounters a woman caught in the act of adultery and famously tells the men who would stone her, “Let anyone among you who is without sin be the first to throw a stone at her” (John 8:7 NRSV).

French is fascinated by the “material tradition” of the pericope adulterae—that is, why the story appears in some early manuscripts of John and not others, as well as pictorial representations of the story on two Coptic pyxides, or small decorated jars—and what that implies about the origins of the story, and about differing practices among communities of believers in the early Christian church.

pyxis

A small lidded jar called a pyxis tells the New Testament story of the pericope adulterae, or the woman taken in adultery.

Image from Art Resource

“My research was a strange combination of paleography, traditional historiography, art history, and even archaeology,” says French. “The goal at all times was to show how society shapes and influences texts, even sacred texts. To do so, I had to attempt to reconstruct worldviews, moral concerns, social relationships, even patterns of trade.”

For students whose curiosity lingers long after class is over, the Undergraduate Research Opportunities Program provides an ideal combination of structure and guidance from faculty along with freedom to shape the scope and focus of their research projects. As House puts it, UROP offers undergraduates a chance “not just to think outside the box, but to move the box altogether.”