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At Pitt, a Tower de Force

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These days, collaboration is key when it comes to elucidating what’s really happening behind the science, and never has this been more so the case than in systems biology. The University of Pittsburgh’s Biomedical Science Tower 3 is just one example of what collaboration can look like on a grand scale. Erected in 2005 and rising 10 stories above ground, BST3 is a $205 million facility whose occupants — eventually, 50 labs with about 500 personnel — have research interests that include structural, computational, and developmental biology, as well as neuroscience, drug discovery, bioengineering, and vaccine development.

Some of the first labs to move in after the building officially opened in October 2005 were those from the department of structural biology, newly established within the university’s medical school, and the new Drug Discovery Institute, which has been established to study orphan diseases and is one of NIH’s 36 new small molecule screening centers.

Today’s advances in genomics and proteomics discoveries require a more collaborative laboratory environment, and BST3 was built to stand as a model for the future of this type of interactive research. To create such an environment, Pitt has taken advantage not only of its place as a major medical teaching and research institution, but also of the state’s biotech sector. With capabilities for studying the genetic causes of diseases and performing advanced imaging, as well as housing one of the few university-based drug discovery programs, BST3 is poised to go beyond simply the concept of systems biology.

According to John Lazo, director of the Drug Discovery Institute and former chair of the medical school’s department of pharmacology, the strength of the institute is that it spans many schools. “That really speaks to the complexity and the dynamic nature of drug discovery,” he says, noting that drug discovery these days requires people from all backgrounds working together, from medicinal chemists to developmental and molecular biologists, to name just a few.

The DDI occupies the ninth and 10th floors of BST3. Working side by side with biologists — structural biology and computational biology occupy the first three floors — means that interaction is bound to happen. “It is hard when you do these cross-discipline type programs to get people to work together,” Lazo says. “So that’s one of the things that we really think is valuable about this particular exercise … actually bringing those people together, and the building lends itself to that.”

Structural biologist Ron Wetzel moved to BST3 last August from the University of Tennessee. He says that until he arrived and settled in, he had no idea just how conducive the space itself would be to his research. As a biologist studying protein aggregation in Huntington’s disease and Alzheimer’s disease, Wetzel has already begun collaborations with computational biologists in an attempt to derive practical applications for advancing drug discovery.

“Computational chemists may be our only hope for getting insights into what the structure of these molecules look like,” Wetzel says, adding that his lab’s long-term goal is to understand the molecular mechanism of one of these neurogenerative diseases.

Academics and Drug Discovery? Really?

“Many people in the field are a little incredulous when you say you’re going to work on a drug discovery program in an academic setting,” Lazo says. Pitt is one of the few academic institutes to house a screening center that rivals an industrial one in sheer magnitude of compounds — up to 100,000 small molecules. But, Lazo emphasizes, the DDI is about discovery, not necessarily making the next Lipitor. “We are really interested in orphan diseases and neglected diseases,” he says. “We’re really trying to focus our efforts on diseases where we have clinical strength.”

And the DDI can do just that, with members coming from four schools at the University of Pittsburgh: medicine, pharmacy, arts and sciences, and public health. Most of these clinicians — nearly 1,400 on the faculty at the medical school and who are logistically close to BST3 — can “bring to the table some very powerful clinical observations, so we want to exploit that,” Lazo says.

Not only are clinicians available to help target markers, but medicinal chemists are in the trenches as well to actually create the small molecules that may one day end up as therapeutics. What Wetzel didn’t have at Tennessee, he has at BST3: connections to synthetic organic chemists. Some of those chemists “are really interested in drug discovery, so much so that they have a more flexible attitude in terms of what kind of molecules they’re willing to try to make,” Wetzel says. “And they’re all integrated into this molecular screening center.”

Joanne Yeh, director of crystallography, is also part of the department of structural biology, which she joined about a year and a half ago after leaving Brown. Her work focuses on resolving the atomic crystal structures of macromolecules. She’s already begun collaborations with Lazo, who is interested in using her work to develop nanobiosensors for assays.

“The type of work we do has a lot of interdisciplinary relevance and implications,” she says. “The molecules that we work on … have a lot of relevance for different disease states [and help] to understand biological mechanisms.” For Yeh, collaboration is key to advancing the application of her work.

“Having researchers within one building with interests that span a wide range of areas and who can work together to study problems and really probe scientific questions is very stimulating,” she says.

While the institute’s high-throughput screening facility is up and running, Lazo’s goal is to see one compound that the DDI discovers be utilized in humans within the next five years. “That’s the hope, and I think there’s a reasonable chance that we can do that,” he says.

Though the brunt of the effort will go toward collaboration to actually screen and produce some of these small molecules, the main goals of the DDI remain research, education, and making drugs not only affordable but accessible. “We’re a little different because we are focused on a product, and that product is tools and new knowledge about chemicals,” Lazo says. And while it can be done partially by separate departments, “we believe [by] bringing everybody together, we can do it a lot better.”

And so it goes for BST3. “I do notice that the faculty here seem to be very open, very much on the lookout for collaborations,” Yeh says. “So it’s a very nice atmosphere for those that want to expand their research.”

 

Name: Biomedical Science Tower 3

Host: University of Pittsburgh

Leadership: Arthur S. Levine, senior vice chancellor for health sciences and dean of the School of Medicine

Staff: 50 labs with about 500 people from various research disciplines

Funding: Design, engineering, and construction of the center cost about
$205 million, which was funded by the university, Pittsburgh Life Sciences Greenhouse, donations, and other sources.

Key research areas: Structural, computational, and developmental biology; neuroscience; drug discovery; bioengineering; and vaccine development

Notable technology: Small molecule screening facility, the world’s largest zebrafish core, a biosafety level 3 lab, and the widest range of NMR instruments in any US lab (600, 700, 800, and 900 MHz magnets)

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