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Stimulating Science

Jef Boeke, right, director of the High Throughput Biology Center, with visitor Elias Zerhouni. HiT Center core technologies are open to all Hopkins investigators.

Elias Zerhouni outlines NIH's "Roadmap" at the official opening of the Research Building on Broadway.

Elias Zerhouni, director of the National Institutes of Health, can talk all he wants about dazzling discoveries made in the lab, but practically everywhere he goes, he says, people always ask him one question: “Where’s the cure?”

To speed up the time it takes for laboratory discoveries to be translated into new medical treatments and drugs, the NIH has proposed a plan called the “NIH Roadmap,” one that Zerhouni outlined on May 25 in Turner Auditorium. The talk kicked off the official opening ceremonies for the Research Building on Broadway, the facility Zerhouni helped plan when he was executive vice dean and vice dean for research at the School of Medicine. On the tours that followed, one place in particular, the newly opened High-Throughput Biology Center on level three, stood out as one that embodies the road map’s key principles.

First and foremost among those principles is advancing our understanding of the combination of molecular events that lead to disease. The sequencing of the human genome has opened up vast opportunities. Scientists now, for example, are trying to learn more about the “proteome,” the set of billions of proteins encoded by an organism’s genome. Finding and analyzing them is such a complex task that they need “high-throughput” technologies, or those that can capture and compare vast amounts of biological data at high speeds.

Four such cutting-edge technologies now are available or planned in the High Throughput (HiT) Biology Center. The Microarray Core contains gene analysis tools that allow scientists to survey the expression of thousands of genes at one time and compare multiple samples. Innovative tools in the Proteomics Core enable researchers to determine how thousands of proteins change from cell type to cell type or normal tissue to disease. In the Sequencing Core, it is possible to build any one of millions of possible tiny DNA fragments or proteins. Chunks of DNA can be sequenced by the thousands daily. The ChemCore will allow researchers to screen a plethora of diverse compounds, gain access to compound libraries and develop assays, or ways to test their favorite biologic process, when it opens later this summer.

Overseen by the Institute of Basic Biomedical Science, the entity that links the School of Medicine’s eight basic science departments, these core services are open to all Hopkins investigators on a fee-for-service basis. Available to researchers on site is one of the Welch Medical Library’s new “touchdown suites,” manned by the Welch’s liaison for the basic sciences, Brian Brown. Also within the HiT Center are analysts specially trained in the use of complex software packages and statistics. “Your average investigator isn’t too strong on statistics, and when you’re getting thousands of results, you have to figure out what’s meaningful,” says Jef Boeke, center director. “People are catching on to the fact that we have staff here to help them analyze the material and train them to use the software. We are eager to collaborate with others on campus.” Currently, the analysts staff only the Microarray Core, but Boeke expects their services will expand to analyze data from the Chem Core and Proteomics Core.

To capitalize on these core technologies, the HiT Center has brought new faculty experts on board. Seth Blackshaw, newly arrived from Harvard, studies the network of genes that control the complex process of development of the mouse retina. Recently recruited from Yale, Heng Zhu co-invented high-density protein microarray technology, a proteomic chip that can analyze lots of proteins all at once. Among other things, the chip can screen for protein targets that drugs can bind to. “Its advantages are that it is very high-throughput and very versatile,” says Zhu. “Assays can be used to analyze all kinds of activities. It opens a new way to study proteomics.”

In addition to penetrating the molecular pathways that lead to disease, the NIH Roadmap seeks to pave the way for more team science. Interdisciplinary groups of researchers already are at work throughout the entire Research Building on Broadway. The McKusick-Nathans Institute of Genetic Medicine, on levels four and five, unites nine centers and scores of researchers from different departments studying human and medical genetics. On levels six and seven, the Institute for Cell Engineering combines researchers from four basic science divisions: stem cell biology, neuroregeneration, immunobiology and vascular cell reengineering.

The HiT Center comprises five different labs in a variety of disciplines. Collectively, the faculty and core facilities represent five basic science departments. Boeke, for example, is a geneticist who studies yeast. His lab is adjacent to that of Min Li, a neuroscientist who studies potassium channels. Indeed, the center itself sprang from a three-way collaboration among researchers when Boeke, Joel Bader, a computational biologist who is one of the center’s five faculty members, and Forrest Spencer, a scientist in the Institute of Genetic Medicine, got together in order to map all the genetic interactions in a yeast cell. “That crystallized for me the idea of a high-throughput center,” says Boeke.

Even in its architecture, the new research building epitomizes collaboration. On the six floors of labs, the long rows of benches have few, if any, walls to separate them. In a couple of years, the Broadway facility will be joined by the Basic Science Building, which is currently under construction across the street on Madison. It, too, will be designed in such a way to bring together new and interdisciplinary research teams.

Exactly what these teams will look like and precisely what projects they will take on is impossible to predict, said Zerhouni. “Research has to come from investigators. You can’t dictate what the ideas will be.” Much like the three-way research partnership that led to the HiT Center, “interdisciplinary teams,” he says, “simply evolve.”

Anne Bennett Swingle



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