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Little State, Big Dreams


As far as research institutes go, the Delaware Biotechnology Institute had an unusual birth. First established in 1999 and formalized with its own building in 2001, the institute was formed as part of a statewide economic development program. "The idea was really to support Delaware's economy by promoting life science type businesses and healthcare," says Kelvin Lee, who took over as director of the institute last fall. "Historically, Delaware has been a base initially for the chemical industry [and later] the credit card industry. There hasn't been a long history of biomedical excellence."

In a partnership that spanned the state's universities and private companies including AstraZeneca and DuPont, the DBI took shape. Because it wasn't founded with a specific scientific purpose in mind, Lee says the scientists who are members of the institute — officially an arm of the University of Delaware — hail from a broad range of research interests, from biofuel to proteomics to plant molecular biology to human health studies of cancer and cardiovascular disease. "The key thing that ties us all together is we're all working in life science," Lee says.

Rather than leading to a lack of direction, that range of interests serves to spark great collaborations, according to scientists at DBI. "It mixes scientists with various expertise," says Pam Green, who joined the institute seven years ago and developed the plant biology concentration there. "For me it's provided a really good environment to cross over system boundaries — to work with vertebrate and invertebrate systems," she adds. "We get a lot of ideas from each other that we never would have had."

Ulhas Naik, whose lab focuses on the role of two proteins in thrombosis and in cancer, says that the institute's breadth "fosters the interdisciplinary research. We have plant people there, we have scientists working on human health, people working on microRNAs, people working on microbiology, plus genomics, proteomics, and bioinformatics," he says. "All these are under one roof."

The collaborative environment seems to be working. Naik is helping to set up a cardiovascular research group that involves the institute as well as the University of Delaware, the local Christiana Hospital, and a Nemours research center.

Traditional (but not)

Another factor that lends the DBI a unique atmosphere is its location: in a technology park just at the edge of the university's campus. "That gives us an interesting feel," Lee says. Being placed in a technology park, he says, makes it easier for faculty to establish partnerships with local biotech companies — being nestled in the middle of an academic campus might not have that effect.

That's not to say that the institute is free of all signs of academia. The staff includes some 15 faculty members, all of whom have joint appointments in regular university academic departments. Lee says in that respect, he's "a traditionalist. The traditional disciplines are there for a reason." He sees a clear advantage to faculty members making the most of what regular academic departments and lab environments have to offer — his own appointment is in chemical engineering — while also availing themselves of the collaboration opportunities and top-notch shared resource facilities in the biotech institute.

Lee relies on the institute's faculty to determine the best research direction, rather than trying to enforce any kind of top-down mandate. Scientists largely fund their own projects, with much of those grants coming from NIH and NSF. The institute's operating costs are paid for with the help of commitments from the state of Delaware.

While Lee is loath to tell scientists what to focus on, he does try to foster a spirit of openness. Pam Green says that Lee encourages institute-wide meetings to help keep members apprised of what the others are doing. "That's very important," Green says.

Down to details

Green's lab focuses on mRNA decay, and her early work with next-gen sequencing systems made her a pioneer in studying noncoding RNA expression in plants. (Green collaborates with Illumina for next-gen -sequencing on some of her projects, but she actually began working with a very young version of the technology back when it was in the hands of Lynx, which eventually merged with Solexa.)

In work with Blake Meyers, a fellow member of the DBI, Green has been doing "a lot of high-throughput sequencing of small RNAs," she says. "We try to use that to profile small RNAs and try to understand their role. Our primary system is plants but [we use] some marine invertebrates as well." Green's biological interest is in parsing out how environmental stressors — drought, high temperature, changes in nutrient availability — "affect how plant genes are regulated post-transcriptionally," she says.

In a recent advance, Meyers and Green demonstrated a procedure to sequence the ends of broken RNAs as a way to track possible cleavage products of microRNAs. "This is opening up a whole new door to understand the targets of microRNAs," she says.

Green adds that this collaboration — Meyers, she says, does the heavy lifting of computational analysis for all this research — "was something that developed just because of this institute. … All that emerged from that proximity and that common interest," she adds.

Not far away, Ulhas Naik is busy with his cardiovascular and cancer research. He studies thrombosis in particular, trying to shed light on what causes platelets to stick in arteries and build a clot that eventually blocks blood flow. About 10 years ago, he says, he managed to clone two proteins that appear to play a role in platelet aggregation.

Naik has continued the work of elucidating those proteins using cell-based assays, RNA interference techniques, and knockout animals. After testing in the cell-based system, he says, the team moved to studying arterial injuries in wild type and knockout mice to help determine precisely how blood clotting functions in the presence or absence of the proteins.

Those same proteins have also been implicated in cancer, Naik says. They appear to be involved in regulating cancer cell metastasis, so he and his lab are also using presence and absence of protein studies to watch how cells metastasize. Naik says that a benefit to being affiliated with DBI is the access to cutting-edge technologies. "That helps me develop new techniques" for establishing the function of these proteins, he says.

Delaware Biotechnology Institute

Newark, Del.

Director: Kelvin Lee
Established: 1999
Key players: The institute ushered in a collaboration across various organizations in the state, including the University of Delaware and Delaware State University, Wesley College, Christiana Care Health System, Alfred I. DuPont Hospital for Children, and more.
Facility: A 72,000-square-foot building for the DBI was dedicated in April 2001
Staff: About 140 total staff, most of whom are students or postdocs. The institute houses about 15 faculty members who all have appointments in academic departments as their tenure homes.
Funding: The main research funding comes through the faculty members. The state of Delaware committed funds to the institute, which are used for operating costs. Other investments have come from AstraZeneca, E.I. DuPont de Nemours, the Kresge Foundation, and others.
Core labs: The institute houses a number of shared facilities, including labs for bioimaging, cellular proteomics, mass spec, bioinformatics, microarrays, and plant growth chambers.

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