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Under One Roof: Big Biology in the Big Apple

By Meredith W. Salisbury

The core facilities alone should make you think about leaving your job. At the Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center’s research branch, some 75 investigators enjoy the use of no fewer than 31 cores. “Sloan-Kettering core facilities are about as good as they get,” says institute Director Thomas Kelly. “We spend about $30 million a year on [them].”

That’s not just a way to teach investigators to share. At the New York-based SKI, core facilities are a critical part of both bringing in bleeding-edge technologies and attracting top recruits in the cancer research field. The cores, which run the gamut from proteomics to sequencing to bioinformatics and are all operated by PhD-level staff, are a cost-effective and efficient way to deliver new tools to institute scientists. “Sophisticated technology is becoming an increasingly important part of what we do,” Kelly says. It’s also essential to keep SKI’s scientists “on the cutting edge of their disciplines,” he adds.

Having the technology on hand is also a good way to lure new scientists to the institute. To that end, a major initiative at the SKI for the past several years has been the drive for a brand new facility, which materialized as a 528,000-square-foot high-rise on the Upper East Side of Manhattan. Part of a $1 billion capital drive launched by Memorial Sloan-Kettering two and a half years ago, the building will serve the twin purposes of boosting recruits and allowing the institute “to expand our basic and translational research and expand the areas of scientific focus,” says Kelly, who expects to begin moving in next month. The additional space will enable SKI to increase its faculty by 50 or 60 — almost doubling the current number of investigators.


The Kelly Plan

It’s not often that the director of an established, 60-year-old research institution gets the green light for an overhaul that’s almost as exhaustive as starting from scratch, but that’s exactly the proposition that the Sloan-Kettering Institute offered Kelly nearly four years ago when they recruited him to be the new director.

Kelly, who had been a faculty member at Johns Hopkins since 1972, leaped at the opportunity to head up the SKI and lead its expansion into the new research facility. First on the to-do list was restructuring how the existing research programs fit together. Under Kelly’s vision for the SKI, the institute added programs in developmental biology, cancer biology and genetics, and computational biology. The existing chemistry and chemical biology division was expanded — so much so that the institute is still heavily recruiting for the program and has devoted the top floor of its new research building to synthetic chemistry.

Then, of course, came the need to encourage interaction between scientists in the different research programs. Having so many core facilities is one way to accomplish that, but the solution can’t come “from the top down,” Kelly says. “You just have to create an environment where people begin to talk to one another.” To that end, each of the eight research programs hosts a weekly lunch, open to anyone in the institute, where faculty members present their research. Similarly, SKI late last year began a seminar program featuring monthly talks from institute investigators.

Another avenue that has successfully fostered collaboration was the establishment of the Experimental Therapeutics Center, a research division not rooted in any particular program. This center focuses “on drug development and understanding how drugs work across the board,” Kelly says. “It has its own budget and it sponsors meetings to bring basic scientists and clinical scientists who are interested in drug development and drug action together.” One key decision was to give the center a grant award program, through which scientists who have agreed to collaborate can apply for seed funding. “There’s really nothing like money to bring investigators together,” Kelly says. While there are no specific plans to start more centers like this, he says this one has been so successful that he anticipates seeing others like it launched in the future.


The Right Tools

Still, plenty of collaborations spark without the benefit of special interdisciplinary centers. Paul Tempst runs the microchemistry and proteomics core facility, which is essentially an outgrowth of his own lab, which focuses on transcriptional regulation. A respected scientist in the proteomics field who just published a much-noted paper on serum peptidomics, Tempst tries to look beyond the tools that define proteomics to take a larger view of his and others’ research. “You can’t have a lab where you only have mass spectrometers,” he says. “There is no such thing as isolated proteomics.” The field ties into molecular, developmental, and cellular science, he says, and through the core facility he runs, he gets to work with many scientists who come from those research areas and are interested in harnessing the power of proteomics. Some of the projects that come into the proteomics core are so intriguing or require the development of new techniques that Tempst and his staff of 14 wind up spending months teamed up with investigators to solve them.

Fine-tuning proteomics applications is a big part of Tempst’s specialty. Through his own lab’s research, he says, “I’m always evaluating and testing the waters of how you can do some applications where you use proteomics. … If people come to me with a certain project, I can say, ‘Well, we’ve done that some time ago and this is how you should do it.’” His lab particularly relies on MALDI-TOF, TOF/TOF, and LC/MS/MS for the protein identification and posttranslational modification experiments it runs.

Unlike some proteomics stalwarts, Tempst says that his approach to proteomics will take advantage of whatever technology works best — rather than relying on the accepted tools of the field. “For me, [a mass spectrometer] is like a car,” he says — a tool to get you “from point A to point B. I’m very open to alternative platforms like antibody arrays,” he says. Case in point: Tempst, who says he’s not “a computer jock,” prefers to use existing platforms to deal with proteomic data rather than figuring out how to code things himself. That led him to use GeneSpring, a software program designed to handle microarray data. Colleagues were appalled by such barrier-crossing, he says, “but if you line up peaks it’s just like comparing spots, so you can use the software and do the statistics.”

Proteomics certainly doesn’t corner the market on bringing in new technologies. Kelly says that investigators are constantly on the lookout for new tools and often make recommendations to the institute about which to bring in-house. He won’t predict “the next gadget” that will pop up at Sloan-Kettering, but does say tools that help understand genetic changes in cells will be of particular interest to the institute. “One of the major efforts [in cancer research] has been to identify genetic changes in cells that lead to cancer,” he says.

Scientists currently use high-throughput methods such as DNA sequencing, genotyping, and microarrays for this, but Kelly predicts that better technologies will be needed in the future. “It’s going to probably require significant improvements in the technology for the high-throughput analysis of the sequence of our genes,” he says. “Once you have that information, then in order to apply that to patients we’re going to have to develop diagnostic methods that are high-throughput that can look at a significant fraction of genes in a tumor, for example, and try to match the genetic changes up with the appropriate therapy.”


Name: Sloan-Kettering Institute

Host: Memorial Sloan-Kettering Cancer Center

Director: Thomas Kelly

Began: Founded in 1945 by Alfred P. Sloan and Charles Kettering;
became part of the Memorial Sloan-Kettering Cancer Center in 1980

Staff: 77 investigators, 365 research fellows, and 140 graduate students

Funding stats: SKI enjoys a sizeable research budget, currently at $278 million. Funding is split fairly evenly, about half from government grants and contracts and the other half from industrial agreements, royalties,
and private donations. The single largest government funding source is
the National Cancer Institute.

Key research areas: Sloan-Kettering scientists are divided into eight research programs, including cancer biology and genetics; cell biology; computational biology; developmental biology; immunology; molecular biology; molecular pharmacology and chemistry; and structural biology.

Core facilities: SKI has 31 core facilities, or slightly better than one for every three investigators. Ranging from glassware washing to X-ray crystallography, the cores include facilities for bioinformatics; DNA sequencing; genomics; microchemistry and proteomics; and NMR.

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