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$40 Million Award to Launch Lab for Protein Discovery

Harvard University has received a federal contract of more than $40 million over the next five years to establish a laboratory at HMS that will speed the search for proteins involved in disease and identify agents that can manipulate them. The contract is through Science Applications International Corporation in Frederick, Md., the operations and technical support contractor for the National Cancer Institute.

Stuart Schreiber is director of the new Molecular Target Laboratory. Photo by Graham Ramsay

The Molecular Target Laboratory (MTL) will build on the efforts of the Harvard Institute of Chemistry and Cell Biology (ICCB), a collaboration created in 1997 between the Faculty of Arts and Sciences and the Faculty of Medicine to develop the field of "chemical genetics," using small molecules to explore protein function in biology. The target laboratory will provide the means to develop chemical genetics in a more systematic way, with the aim of identifying specific small-molecule probes for every gene product potentially relevant to cancer.

Such probes will complement the knowledge generated by genomics and proteomics research. This work identifies large networks of proteins that may be involved in human pathology, but it becomes increasingly difficult to tease out which of the many candidate proteins is the key to a particular disease. The MTL's long-term aim is to provide a comprehensive, publicly accessible database of chemicals with useful biological effects, making it possible for researchers studying a cellular process to identify which proteins are the key control points.

The target laboratory will contain facilities to synthesize and study libraries of small molecules with properties unprecedented for synthetic compounds--properties more reminiscent of naturally occurring small molecules. It will produce and collect stock solutions of these molecules and develop a "library of libraries," a clearinghouse for all the libraries of molecules currently being developed by individual labs. It also will house screening technologies for quickly identifying molecules of interest based on the proteins they bind to and other properties. The MTL will have the capacity to conduct studies on a much larger scale than has been done before. According to Stuart Schreiber, the Morris Loeb professor of chemistry and chemical biology at Harvard University and director of the new lab: "The defining feature of the MTL will be the advent of a systematic approach to chemical genetics."

An important part of the target laboratory's mission is that the discoveries it generates will be publicly available and accessible to all researchers. "The primary product of this systematic approach is a public database," Schreiber said. This database will be a significant resource for scientists, analogous to GenBank for genes. "Such a database becomes a discovery engine and a hypothesis-driving mechanism," he added. Because of the vast amount of information such a process will generate, part of the target laboratory's work will be to integrate chemical genetics with information science and genomics to make the data accessible and useful.

Like the Institute of Chemistry and Cell Biology, the MTL's approach is a marriage of biology and chemistry, involving researchers in both fields. Just as the use of chemical modulators can demonstrate protein interactions in the cell, the biological studies also will shed light on the chemistry of these molecules. According to Rebecca Ward, director of research affairs at the ICCB, "The systematic approach of the MTL will allow researchers to develop a very broad picture of what different chemicals can do."

--Courtney Humphries