NIH launches first center in Nationwide Chemical Genomics Network

06/09/04

Initiative will generate new tools to accelerate study of human disease

BETHESDA, Md., Wed., June 9, 2004 The National Institutes of Health (NIH) today announced the establishment of the NIH Chemical Genomics Center the first component of a nationwide network that will produce innovative chemical "tools" for use in biological research and drug development.

"Providing public-sector researchers with this unprecedented opportunity will greatly broaden the scope of biological exploration," said NIH Director Elias A. Zerhouni, M.D. "The NIH-supported chemical genomics network will have a transformative effect on medical research by expanding our understanding of how the human genome and proteome function, which in turn will speed the development of new ways to fight disease and improve human health."

In contrast to researchers in the pharmaceutical industry, many academic and government scientists currently do not have easy access to large libraries of organic chemical compounds. Such compounds, which scientists call "small molecules" because they are smaller than proteins, can be used as tools to modulate gene function and improve understanding of biological pathways involved in human health and disease. This area of research is often referred to as chemical genomics.

Established through the Molecular Libraries and Imaging working group of the recently announced NIH Roadmap for Medical Research, the NIH Chemical Genomics Center is based in the National Human Genome Research Institute's (NHGRI) Division of Intramural Research. It is the first component of an initiative that will result in a consortium of chemical genomics screening centers. In addition to NHGRI, the National Institute of Mental Health (NIMH) is providing leadership for this initiative, which, like all of the Roadmap initiatives, includes representation from numerous NIH institutes and centers.

Up to 10 pilot centers will be funded at academic institutions and other locations across the country in Fiscal Year (FY) 2005. "These chemical genomics centers will be coordinated to build a network in the academic research community for identifying a broad range of small molecules with promising properties for biological research," said NIMH Director Thomas R. Insel, M.D.

To support the network, NIH plans to establish a repository to acquire, maintain and distribute a collection of up to 1 million chemical compounds. As was the case for the Human Genome Project, data generated by the chemical genomics network will be deposited in a central database, called PubChem, which will be managed by the National Center for Biotechnology Information at the National Library of Medicine and will be freely available to the entire scientific community.

"Our effort will build upon what has been learned by the pharmaceutical industry, but it should not be viewed as an effort to turn public sector researchers into drug developers," said NHGRI Director Francis S. Collins, M.D., Ph.D. "What we are doing is simply giving academic and government researchers a chance to contribute in a much more vigorous way to the earliest stages of the drug development pipeline: the identification of useful biological targets. This is a win-win situation for basic biology, for the drug industry and, most importantly, for the American public."

Christopher P. Austin, M.D., who is NHGRI's senior advisor for translational research, will direct the NIH Chemical Genomics Center. The center, which will have a staff of about 50 scientists, plans to begin high-throughput screening of small molecules by the end of 2004.

While most marketed drugs are small molecules and this class of chemicals has been the focus of intense screening efforts by the pharmaceutical industry for many years researchers in academia, government and non-profit research institutions traditionally have not been able to tap into large libraries of these compounds. In addition, pharmaceutical research tends to focus on small molecules that act upon a relatively narrow group of molecular targets with known relevance to human disease. The chemical genomics center network will explore the vast majority of the human genome for which no small-molecule chemical probes have been identified. Of the hundreds of thousands of proteins thought to be encoded by the 25,000 genes in the human genome, less than 500 currently have a chemical compound with which they interact.

With an eye toward expanding the frontiers of genomic exploration, the NIH Chemical Genomics Center plans to screen more than 100,000 small-molecule compounds in multiple high-throughput assays within its first year of operation. "Screening on the scale we are planning is unprecedented outside of the pharmaceutical and biotechnology industries. For the first time, biologists in the public sector will be able to take full advantage of the tremendous power of small molecules to serve as probes to advance our understanding of biology," said Dr. Austin.

To help achieve its ambitious goals, the NIH Chemical Genomics Center has selected a suite of ultra-high throughput target and pathway screening technologies from Kalypsys, Inc. of San Diego. The Kalypsys agreement, valued at up to $30 million over the course of a four-year contract if all options are exercised, will deliver to the NIH center a suite of technologies, materials and services, including a highly automated robotic system capable of screening more than 1 million compounds per day in a variety of biochemical and cellular assays.

The Kalypsys system features an innovative, rapid parallel assay process that uses proprietary robotic and liquid-handling technologies to dispense cells or proteins onto 4x6 inch plates, each containing 1,536 microwells. The system then transfers a different chemical compound into each well, and the wells are examined by computerized scanners to assess the effect of each compound on the cells or protein. For example, one compound may activate a particular function in a cell, while others may have the opposite effect or no effect at all. In addition to cells and proteins, the Kalypsys system will offer researchers the ability to screen small, whole organisms, such as zebrafish embryos or yeast, against a large array of chemical compounds. A high-resolution photo and a low-resolution video of the Kalypsys system are available at: http://www.genome.gov/10005141.

Data gleaned from the screening effort will shed new light on the function of various genes and the roles that specific genes play in pathways crucial to biological function. Ultimately, researchers hope the information generated by the chemical genomics network will identify new targets for therapy and tools to study them, thereby enabling such targets to move more rapidly through the drug development pipeline.

Also today, Dr. Austin announced that Jim Inglese, Ph.D., has been appointed head of biomolecular screening in the NIH Chemical Genomics Center. "We are very excited that a researcher of Dr. Inglese's stature in the pharmaceutical and chemical genomics communities is joining our team. His expertise in high-throughput screening technologies and assay development will be a tremendous asset to our center," said Dr. Austin, noting that Dr. Inglese comes to NHGRI from Merck Research Laboratories in North Wales, Pa., where he was a senior research fellow in the automated biotechnology group.

Dr. Inglese received a B.S. in Chemistry from the Rensselaer Polytechnic Institute, Troy, N.Y., in 1984, and a Ph.D. in Organic Chemistry from Pennsylvania State University, University Park, Pa., in 1989. He is the founding editor and editor-in-chief of the peer-reviewed journal, ASSAY and Drug Development Technologies.

About the NIH Roadmap for Medical Research

The NIH Roadmap is a series of far-reaching initiatives designed to transform the nation's medical research capabilities and speed the movement of research discoveries from the bench to the bedside. It provides a framework of the priorities the NIH must address in order to optimize its entire research portfolio and lays out a vision for a more efficient and productive system of medical research. Additional information about the NIH Roadmap can be found at its Web site, http://www.nihroadmap.nih.gov.

About NHGRI

NHGRI is one of the 27 institutes and centers at NIH, an agency of the Department of Health and Human Services. The NHGRI Division of Intramural Research develops and implements technology to understand, diagnose and treat genomic and genetic diseases. The NHGRI Division of Extramural Research supports grants for research and for training and career development at sites nationwide. Additional information about NHGRI can be found at its Web site, http://www.genome.gov.

About NIH

The NIH comprises the Office of the Director and 27 Institutes and Centers. The Office of the Director is the central office of the NIH and is responsible for setting policy for the NIH and for planning, managing, and coordinating the programs and activities of all the NIH components. The NIH is a component of the U.S. Department of Health and Human Services. Additional information about the NIH can be found at its Web site, http://www.nih.gov.

Source: Eurekalert & others

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