The NIH Roadmap, a massive undertaking by the National Institutes of Health that began with a series of meetings initiated in 2002 by NIH Director Elias A. Zerhouni, MD, has now taken on form and meaning for the biomedical research community. Of particular interest to SBS members are the Molecular Libraries and Imaging initiatives now underway (see http://www.nimh.nih.gov/dnbbs/73-mcrm.cfm) and the June, 2005, issue of SBS News. These initiatives will offer the academic and non-profit sectors unprecedented access to the latest assay and screening technologies, and will also provide opportunities for industry.

Because of the importance and evolving nature of these new initiatives, SBS has made a commitment to NIH to help communicate information about RFAs, funding opportunities, new databases, and other resources for the chemical genomics and drug-discovery communities. Information will be available on an ongoing basis in this section of the SBS web site and in SBS News, e-wires, and other publications.

NIH Roadmap’s Molecular Libraries Screening Centers Network Established

Nine Screening Centers in Seven States

The NIH announced on June 15, 2005 that it has awarded $88.9 million in grants to nine institutions over three years to establish a collaborative research network that will use high-tech screening methods to identify small molecules that can be used as research tools. Small molecules have great potential to help scientists in their efforts to learn more about key biological processes involved in human health and disease.

"This tremendous collaborative effort will accelerate our understanding of biology and disease mechanisms," said Elias A. Zerhouni, M.D., NIH Director. "More importantly, it will, for the first time, enable academic researchers to explore novel ideas and enable progress on a broad front against human disease."

For example, the broad-based screening effort will eventually enable researchers to explore the hundreds of thousands of proteins believed to be encoded by the approximately 25,000 genes in the human genome. To date, only a few hundred human proteins have been studied in detail using small molecule probes.

Certain small organic chemical compounds, also referred to as small molecules, can be valuable tools for understanding the many important cellular events involved in health and disease, which is key to identifying possible new targets for diagnosis, treatment and prevention. To date, most useful small molecules have been found serendipitously. The molecular libraries screening program is an effort by NIH to take an efficient, high-throughput approach toward the discovery of many more useful compounds.

The Molecular Libraries Screening Centers Network (MLSCN) is being developed through the NIH Roadmap for medical research. Specifically, the network is part of the Roadmap's "New Pathways to Discovery" initiative, which has set out to advance the understanding of biological systems and build a better "toolbox" for medical researchers in the 21st century.

The network is funded by all of the institutes of the NIH and co-administered by the National Institute of Mental Health (NIMH) and the National Human Genome Research Institute (NHGRI) on behalf of NIH. The operation of the network will be overseen by a project team made up of staff from NIH's 27 institutes and centers.

Data generated from the high-throughput assays conducted at the screening centers will be made available to researchers in both the public and private sectors through the PubChem database (http://pubchem.ncbi.nlm.nih.gov/), created and managed by the National Library of Medicine at NIH.

The network's first screening center, the NIH Chemical Genomics Center (NCGC), was established in June 2004 by the NHGRI's intramural program to jumpstart the roadmap effort. Another critical component of the network is the Molecular Libraries Small Molecule Repository, located in San Francisco at Discovery Partners International, a drug discovery research firm. The repository houses the collection of small molecules that will be used for screening by the centers. Already, the repository has acquired nearly 100,000 compounds that are being utilized by the NCGC.

"This new Screening Centers Network will be the engine of discovery in the NIH Roadmap Molecular Libraries initiative," said NIMH Director Thomas R. Insel, M.D. "Using the compounds from the Molecular Libraries Small Molecule Repository and supported by the informatics capabilities of PubChem, the MLSCN should provide researchers with many new chemical tools to explore how cells function at the molecular level."

"This collaborative screening effort will enable academic and government researchers to contribute in a much more vigorous way to an understanding of the mechanisms of disease, and even to the identification of potential targets for new therapies. Central to this effort are the databases supporting the network, which will allow us to tie together data from diverse fields of science in ways not previously brought to bear on important health problems," said NHGRI Director Francis S. Collins, M.D.,Ph.D.

The nine institutions receiving grants as part of the Molecular Libraries Screening Centers Network (MLSCN) are:

• Columbia University Medical Center, New York, New York; James Rothman, Principal Investigator; MLSCN Center at Columbia University
• Emory University, Atlanta, Georgia; Raymond Dingledine, Principal Investigator; Emory Chemistry-Biology Center in the MLSCN
• Southern Research Institute, Birmingham, Alabama; Gary Piazza, Principal Investigator; Southern Research Molecular Libraries Screening Center (SRMLSC)
• The Burnham Institute, La Jolla, California; John Reed, Principal Investigator; San Diego Chemical Library Screening Center
• The Scripps Research Institute, La Jolla, California; Hugh Rosen, Principal Investigator; Scripps Research Institute Molecular Screening Center
• University of New Mexico Albuquerque, Albuquerque, New Mexico; Larry Sklar, Principal Investigator; New Mexico Molecular Libraries Screening Center
• University of Pennsylvania, Philadelphia, Pennsylvania; Scott Diamond, Principal Investigator; The Penn Center for Molecular Discovery
• University of Pittsburgh at Pittsburgh, Pittsburgh, Pennsylvania; John Lazo, Principal Investigator; University of Pittsburgh Molecular Libraries Screening Center
• Vanderbilt University, Nashville, Tennessee; C. David Weaver, Principal Investigator; Vanderbilt Screening Center for GPCRs, Ion Channels, and Transporters

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