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Translational Medicine at Scripps Florida

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When Scripps Florida was first envisioned, some scientists imagined that it would become a model for how to merge basic biomedical research with a drug discovery environment to take advantage of the best minds and technologies while shaving years off the typical drug timeline. What they didn’t imagine was that the institute would first become a model for how to perform high-level science in a shifting political landscape with less-than-ideal resources.


Three years ago, the Scripps Research Institute in La Jolla, Calif., struck a deal with the state of Florida that gave the institute an East Coast foothold and promised hundreds of biotech jobs for the region. That promise came along with a $310 million appropriation from the state legislature for the institute, and in January 2004 the new entity, Scripps Florida, was officially opened. It would be situated in Palm Beach County, where the local government was to fork over a hunk of land and pay for construction of the new facilities.


But the sense of mutual triumph ended when an environmental lawsuit was filed to prevent Scripps Florida from building on the land Palm Beach County had selected for it. Since then, researchers at the fledgling institute have engaged in great science under what some would consider adverse conditions. Many of the labs are in temporary building space granted to them by Florida Atlantic University, while the administrative and bioinformatics staff members have been working out of trailers, says Harry Orf, vice president of scientific operations for Scripps Florida. Orf says the institute is about two years behind schedule due to the lawsuit, which was finally resolved when the county found a more acceptable site for the new facility.


Currently, the first group of labs is situated in a new building on the university’s Jupiter, Fla., campus; another new building was set to open late this summer to house more of the Scripps Florida team. Eventually, those buildings will be given back to the university for its own faculty, and the Scripps Florida people will move to a nearby 350,000-square-foot, three-building compound for which construction is slated to begin this December.


Lay of the land


Now that the legal battles appear to be over, all eyes are on the science, which has been quietly but surely underway since 2004. The concept behind Scripps Florida, says Orf, “is to combine basic biomedical research with an advanced technologies component and have a focus on a drug discovery platform.” To that end, the institute has two academic departments — one for biochemistry and one for infectious disease — as well as the Translational Research Institute, which houses the advanced technologies and drug discovery initiatives.


On the academic side, things are fairly traditional, with faculty appointments, postdocs, and a PhD program. “It’s very much like a classic academic biomedical research institute,” Orf says.


The Translational Research Institute is Scripps Florida’s endeavor to build a public-sector drug discovery environment — and much of it relies on a collection of big-ticket, cutting-edge systems biology tools. Jennifer Busby, who runs the proteomics core, has been buying equipment since her lab first opened in a temporary building two years ago. Though she has plenty of mass spec and other tools to perform the post-translational modification and additional proteomics work requested by many of the Scripps faculty members, she’s looking forward to moving to the permanent facility, where she will have enough space to install technologies such as an FTMS. “Now we have the light at the end of the tunnel,” she says of the recent approval for the new Scripps location. “That does help in terms of deciding longer-term projects.”


Busby has collaborations with people from Scripps Florida, Scripps’ La Jolla headquarters, and elsewhere. Like the other core facilities in the advanced technologies division, her lab straddles the basic research/pharma divide, so she helps scientists from all parts of the institute. She also works with scientists from the other core facilities at Scripps Florida to answer some of the larger questions people are asking. “Many of the … faculty are using all of the cores available to them,” she says. Because the core labs are “literally all in the same hallway,” she says there’s a good deal of cooperation, such as working together on samples, to help get investigators the best results for their research.


Developing discovery


What makes Scripps Florida unique among biomedical research institutes is its drug discovery effort, which covers the major “steps of translational research that are otherwise relegated to biotech or pharmaceutical companies,” says Harry Orf. Those include target identification, lead compound identification, and lead compound optimization.


The Translational Research Institute is headed up by Patrick Griffin, a mass spec expert who has worked for Lee Hood and Don Hunt and spent 11 years at Merck. Griffin says his experience in pharma taught him that “you need to be critical of the program so you don’t keep [a target or compound] going beyond its acceptable life span,” he says. He also says team integration is essential: “There’s no way to do lead optimization in a single-investigator lab.”


The organization follows a recognizable pharma model, with groups for discovery biology, medicinal chemistry, drug metabolism and pharmacokinetics, pharmacology, informatics support, and lead identification. What will be different: scientists from the basic research branch might work directly with the discovery biology group, and targets from the basic side could be put into the pipeline at the high-throughput screening point, Griffin says.


Griffin and his team have a number of resources at their disposal, including a compound library with about 600,000 molecules and a high-throughput screening system, in addition to several core labs. The scientists are starting out with neurobiology and cancer as their primary therapeutic areas, and already “we’re making significant progress,” reports Griffin. One effort involves “developing novel strategies for screening [peptide GPCRs] against small molecules,” he says.


According to Griffin, a major advantage for his discovery team is the number of ways to capitalize on their work — rather than just the usual way of making a drug. “We can bring things up to preclinical and that’s about as far as we can go,” he says. “The exit strategies are wide open for us on a program. We might find a partner where we would either continue [development], or we could form a spinout company that takes that compound on board.”


Clearly, hopes are high for Scripps Florida, and the young institute still has a number of years ahead of it just slated for ramping up. That will give scientists there plenty of time to prove the merit of their concept. “This is a unique opportunity to start something from scratch,” says Harry Orf, “and to do something that hadn’t been done in an academic setting.”



InfoSpot


Name: Scripps Florida


Host: Scripps Research Institute


Director: Harry Orf, vice president of scientific operations


Began: January 2004


Staff: 25 faculty and close to 60 staff scientists; the entire institute currently has about 170 people. That could grow to about 1,000 people in the next five or six years as the center ramps up.


Funding stats: The institute kicked off with a $310 million appropriation from the Florida State Legislature to convince Scripps to land its new venture in the Sunshine State. Palm Beach County is also providing an economic package, including the land and funding for construction of the new buildings. Meanwhile, researchers at Scripps Florida have started pulling in large NIH grants, and corporations and nonprofit organizations have pledged million-dollar-plus philanthropic gifts to the institute.


Key research areas: Biochemistry, infectious disease, cancer, neurobiology

Core facilities: Bioinformatics; flow cytometry; cell-based screening; RNA dynamics/gene expression; proteomics; protein production and crystallography; and high-throughput screening