June 2010

The Johns Hopkins Institute for NanoBioTechnology: Small in Science, but Not in Scope

Many universities have been creating multidisciplinary research institutes over the past several years in a reflection of the more collaborative nature of science. Typically, the stories are similar in origin; perhaps a new building, some specialized resources, a directed research vision and, of course, a select group of top-level faculty members who can push that vision forward— in part, by providing a level of prestige that can draw in the lifeblood of research: funding and students.

But, what if this traditional model was turned on its head? Thanks to some forward-thinking scientists at The Johns Hopkins University in Baltimore, we have an answer: the Institute for NanoBioTechnology.

Launched in May 2006, the INBT employs the emerging field of nanotechnology, which manipulates matter at the molecular, or even atomic, levels to design new materials and devices, to both answer fundamental questions about cell behavior and to develop new advances in biomedicine.

At first glance, it may seem like ordinary fare, but a closer inspection reveals that INBT follows its own path.

“If you look past the surface of a typical university-based multidisciplinary research center, you often find that the institute is self-contained and doesn’t spill over to the surrounding academic community at large,” explains Peter C. Searson, the Joseph R. and Lynn C. Reynolds professor of materials science and engineering at Johns Hopkins and director of INBT.

Science-Centric---Directors
Johns Hopkins Institute for NanoBioTechnology Director Peter C. Searson (on left) and Associate Director Denis Wirtz. Photo credit Will Kirk.

INBT’s Associate Director Denis Wirtz, the Theophilus Halley Smoot professor of chemical and biomolecular engineering, completes the thought: “In essence, a traditional research institute is kind of like an exclusive club. The INBT at Hopkins, in comparison, is exactly the opposite; it was designed to be an inclusive club.”

The numbers back that up; just four years after INBT’s launch, the institute has grown to include 212 affiliated members from across the vast Johns Hopkins community. Members hail from the School of Medicine, the Bloomberg School of Public Health, the Krieger School of Arts and Sciences, the Whiting School of Engineering and even the Applied Physics Laboratory.

And, INBT still will welcome more, for it’s as much a social network as a science institute; its purpose is to help Hopkins researchers interested in pursuing nanotechnology find partners or resources for their research, be it biologists who are looking for engineering tools to answer their questions or engineers seeking biological problems for their technology.

NRC Publishes Report on Multidisciplinary Research

The term “multidisciplinary science” constantly is evolving— after all, it wasn’t that long ago when merging the fields of biology and chemistry seemed like a radical concept, whereas today, its common to see scientists who equally are well-versed in genetics, biochemistry and cell biology.

However, as the 21st century marches on, another seemingly radical merger is taking shape as the physical sciences become more prevalent in biology. True, some fields like structural biology have employed principles from physics for many years, but now, scientists from many other traditionally “descriptive” biology fields have been heading towards this life sciences-physical sciences interface. This can be seen from the individual lab to whole universities, such as the Johns Hopkins Institute for NanoBioTechnology highlighted here.

Recently, the National Research Council has shed more light on this growing convergence through the publication of their report, “Research at the Intersection of the Physical and Life Sciences.” Prepared by a committee which included American Society for Biochemistry and Molecular Biology President Gregory Petsko, this report presents three main objectives: 1) to provide a framework for understanding the goals of intersection science and why it is worthy of attention from both scientists and funding agencies; 2) to assess current efforts at combining physical and life sciences and suggest some promising opportunities for future efforts; and 3) to set out strategies to enhance collaboration so that researchers can take full advantage of the opportunities at this intersection.

The report is worth a read by any scientist who currently is, or is considering, carrying out work at the physics-biology interface. As a special offer, ASBMB Today readers will receive a 25 percent discount when they order this report here. To take advantage of the special offer, use the discount code “SASBMB” when you enter your payment information during the purchase process.

Also, be sure to check out this month’s special ASBMB Today companion podcast with Petsko as he discusses, among other topics, the NRC report.

This is a vital resource, because, as scientific disciplines go, nanotechnology is a truly integrative field. It may deal with matter at the smallest scale, but the functional interface between biology, chemistry, physics and engineering is immense.

“Think about all the scientific expertise required to develop gold nanoparticles that can deliver targeted drugs to a tumor,” says Wirtz, citing a common nanotech application. “You need clinical researchers who understand tumor physiology, colloid and interface scientists who can design particles that will work in the bloodstream, molecular biologists to perform in vitro studies, imaging experts to track the particles in vivo and toxicologists who can ascertain if the nanoparticles will be poisonous, just to name a few.”

INBT accomplishes its mission of bringing together interested nanoscientists through a variety of efforts. Its website serves as a welcome center and community portal, providing a list of INBT affiliates and their research interests, relevant funding opportunities, a repository of nanotechnology tools that Hopkins researchers have developed and even an online grant submission assistant.

INBT also hosts an annual symposium on campus that highlights emerging areas of nanotechnology research in health and biology, another networking and educational opportunity that Searson notes is one of the most highly attended scientific events at the university.

The institute even runs annual competitions for pilot project programs, awarding seed money to teams of two or more faculty that propose research ideas spanning the biology-physical science interface.

“These awards are great because, in today’s funding environment, especially when dealing with novel and untested techniques, a good idea is simply not enough,” notes American Society for Biochemistry and Molecular Biology member Pamela Zeitlin, a professor of pediatrics at Hopkins who has been one of many clinicians to join up with the INBT. “These days, you need some proof of the principle, and these small seed grants help researchers get that invaluable preliminary data to support larger grants.”

Last year, Zeitlin, who studies the molecular and genetic underpinnings of cystic fibrosis, teamed up with colleague Neeraj Vij and received a project award to study the potential of inhaled nanoparticles to deliver cystic fibrosis drugs directly to the lungs and avoid potential systemic side effects.

As Searson explains, “Hopkins is an ideal institution for researchers who want to explore nanotechnology in biomedicine, and INBT strives to do the utmost to lower the barrier to entry and encourage them to make that effort.”

Starting Small

In fitting with the nontraditional and inclusive nature of INBT, the origin of this institute is quite unusual as well. It wasn’t a grand design unveiled at the presidential-level, a large philanthropic donation or some other top-down development that led to INBT’s formation. Rather, the vision for this integrative center was a grassroots effort, originating with a small group of researchers who saw an opportunity to connect many of Hopkins’ academic strengths.

Science-Centric---UV-Light
Peter C. Searson’s lab has been developing cadmium selenide quantum dots (specialized nanoscale semiconductors, pictured here fluorescing under UV light) to visualize and track a variety of molecular processes.  Photo by Rich Folkers at NCI.

The genesis occurred in 2004, when Searson and Wirtz began having informal conversations about some interesting areas where they could expand their research. “And about that time, the National Institutes of Health was discussing nanomedicine as part of their roadmap, and we both agreed that biomedical innovations, particularly in drug delivery and medical imaging, would be significant outlets for nanotechnology,” Searson says. “And Hopkins, which is synonymous with outstanding medical research at both the basic and clinical levels, would provide no shortage of connections for that outlet.”

“But, we decided we wanted something more than just us knocking on some biologists’ doors looking for collaborative projects,” he continues. “We began wondering, how could we make a nanobiology initiative happen on a large scale?”

So, Searson and Wirtz gathered up some other like-minded colleagues, such as ASBMB member Peter N. Devreotes in Hopkins’ department of cell biology.

“I thought the idea Peter and Denis presented was wonderful, though not necessarily because of the nanotechnology angle,” says Devreotes, who serves as part of the INBT executive committee. “After all, molecular biologists have been working at the ‘nano’ scale for more than 30 years.”

“However, our biology faculty has this tremendous resource in the outstanding engineering programs at Hopkins, and developing fruitful collaborations between the two groups would really help us advance basic biomedical knowledge, particularly in getting more quantitative information.”

Over the next two years, the INBT initiative slowly moved up the academic ladder, eventually reaching the level of Hopkins’ president and deans, whom they then managed to convince that setting up a nanobiotechnology institute was worthwhile.

And, four years later, the numbers have rewarded that decision. Not only have more than 200 researchers signed on to this undertaking, including many of this university’s most accomplished members, but INBT also already has generated more than $44 million in federal funding, almost triple the expected amount, given the number of submissions.

Among these many grants is the 5-year/$14.8 million award for the Johns Hopkins Engineering in Oncology Center, launched last October as one of the dozen new National Cancer Institute-sponsored Physical Sciences-Oncology Centers, an initiative aimed at pursuing a new avenue of cancer research by studying the physical laws and properties of this disease.

“The award for the EOC exemplifies how having a coordinated institute has helped Johns Hopkins as a whole,” says Searson. “Denis foresaw that new approaches for cancer could be a big NIH focus in the future, so we helped pave the way for that in some of the projects we supported and in making nanotechnology for cancer the focus of our symposium in 2008.”

“We try to anticipate funding trends,” adds Wirtz, “so, by the time we need to make proposals, we already have teams of scientists with experience in that field, as well as a proven record of working together and training students together, so we set up an unbeatable proposal.”

As to where INBT might make its next major impact, Searson notes that discussions are already underway for future initiatives, although he notes, with a smile, that they are “top secret.”

However, he directs all curious individuals to the annual NanoBio symposium. “Remember, we focused on cancer in our 2008 symposium and soon thereafter developed our EOC proposal,” he says. “So, if you want some clue as to areas we think are important, well, neurobiology was the topic of the 2009 symposium, and just last month, we hosted our 2010 symposium on nanotechnology in public health and the environment.”

As for other future plans, INBT actively is looking at increasing corporate and industry partnerships, a vital link considering the commercial potential of nanotechnology and also preparing for a new 18,000-square-foot headquarters on the Homewood campus. For, while INBT remains a bit nontraditional as research institutes go, Searson and Wirtz acknowledge that it cannot be completely virtual, and a centralized location is important to provide physical interactions, especially among students, that can boost collaboration.

Starting Young

Science-Centric---Cells
Denis Wirtz’s group has been using a variety of biological and engineering techniques to study the factors affecting the movement and positioning of the microtubule organizing center relative to the cell center.

But, although this future campus space will provide a central hub for the university-wide INBT, the real glue that holds this institute together is its student and postdoctoral workforce— and not just because they do all of the grunt work.

“The students have been instrumental to our success because they play the matchmaker,” Wirtz notes. “They develop the ideas for cross-disciplinary projects that help bring faculty together.”

For example, Wirtz, who employs particle-tracking technology to study cytoskeleton activity and cell movement, recently had a student propose an idea to use these tracking techniques to monitor viral entry into cells. Knowing very little about viral behavior, Wirtz was nervous about the many potential experimental pitfalls. “But, over at the medical school, we have Robert Siciliano, one of the foremost experts on HIV, so I encouraged my student to talk to him, and soon we had set up a joint effort.” Searson and Devreotes, meanwhile, recently have set up their own joint effort to develop a universal method of tagging cell surface receptors using quantum dot technology.

 

That’s why training initiatives have been a vital component of INBT’s mission. Beyond simply developing better nanobiotechnology tools, they want to create a new breed of scientists and engineers who speak a common language, and who would be equally adept at publishing in both biological and engineering journals.

“We’re not talking about an engineer who publishes an article with some biological applications in an engineering journal,” Searson says. “We’re talking about an engineer who can publish a paper in a top-level biology journal, who can really pass a rigorous peer review of experts.”

To accomplish this, INBT has initiated programs for trainees at all levels, including postdoctoral fellowships in nanotechnology for cancer medicine and summer research opportunities for undergraduates.

A core element, though, is the National Science Foundation-funded IGERT (integrative graduate education and research traineeship) fellowship program. The IGERT program brings together about 6-10 incoming graduate students of various backgrounds each year, and, starting with a 1-week boot camp where senior IGERT fellows provide a crash course on basic principles and techniques in both life sciences and engineering, they undertake classes and seminars to prepare them for multidisciplinary, nanotechnology research; the program includes an open-ended lab course where the students design and develop their own nanoprobes, with the students and advisors working together to tailor the project to the interests of the group.

Afterwards, IGERT fellows are strongly encouraged to find a secondary adviser in a different field to help them become more well-rounded. This co-advising is more than a token effort; the students have lab space and lab responsibilities, such as giving group meetings, for both of their mentors. However, by the time the fellows have completed their requirements, they have learned how to work with people of different backgrounds, developed important skills in critical thinking, gained solid knowledge in a complementary discipline and have developed a strong network of colleagues that, hopefully, lasts beyond Hopkins.

“It definitely has required a little extra work on my part, but it certainly has been worth it,” notes IGERT fellow Laura Dickinson, a student in Sharon Gerecht’s group in the chemical and biomolecular engineering department who studies how various stem cells reprogram and repattern to form functional blood vessels. “I think I’ve gained a better understanding of difficult concepts like surface patterning and quantum dots, and it’s been great meeting students from other disciplines who I can call on for help in case I need it.”

“I think in the near future, such cross-disciplinary training will become commonplace,” Searson says, “and we’ll look back and wonder how we ever taught students before.”

But, it’s not just the students who are breaking down traditional walls.

Searson notes he’s had numerous scientists from around the world talk to him and question how INBT, with so many joint initiatives, handles tricky issues like co-authorship or assigning principal investigators. “And, I tell them it never has been a problem; our members understand the stakes and the great potential of the INBT and are willing to put aside some of their own individual gains.”

Because, sometimes, you just have to break with tradition.

Nick Zagorski (nzagorski@asbmb.org) is a science writer at ASBMB.


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