NIH Launches First Center In Nationwide Chemical Genomics Network|
Initiative Will Generate New Tools to Accelerate Study of Human Disease
Bethesda, Maryland 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
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
"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
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
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, www.nihroadmap.nih.gov.
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, www.genome.gov.
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, www.nih.gov.