NIH Funds Nine Centers to Speed Application of Powerful New Research Approach
News Sep 03, 2008
The network — funded at approximately $70 million annually over the four-year production phase — is designed to increase the pace of development and use of chemical (small molecule) probes, which have become invaluable tools for exploring biologic processes and for developing new therapies for disease.
"This network marks a new era in academic and government research as NIH-funded scientists will have access to the tools for rapidly screening hundreds of thousands of small molecules against many novel biological assays at lower costs than previously possible," said Elias A. Zerhouni, M.D., NIH director. "The information generated by this network will be important to developing a greater understanding of biology and its complexity, while hopefully discovering novel approaches to therapies and prevention, especially for rare or neglected diseases."
As genomics research reveals more about the enormous complexity of cell function, new approaches are needed to understand the details. Small molecule probes can be minutely targeted to interact with one site of a cell’s chemical machinery, thus providing information on a specific step in a cascade of cell functions. In some cases, small molecules may have activity that gives them potential for eventual therapeutic as well as research use; or, they may identify targets in the cell for the design of future therapies.
The Molecular Libraries Probe Production Centers Network is the second phase of a program begun in 2004 as part of the Molecular Libraries and Imaging Initiative (http://nihroadmap.nih.gov/molecularlibraries/) under NIH’s Roadmap for Medical Research. Using assays — laboratory tests used to screen for specific types of probes — solicited by NIH from the research community, the network will screen a library of more than 300,000 small molecules maintained in the program’s Molecular Libraries Small Molecule Repository (http://mlsmr.glpg.com/MLSMR_HomePage/). The repository is located in San Francisco at Biofocus DPI, a drug discovery research company. Data generated by the screening is available to the public through PubChem(http://pubchem.ncbi.nlm.nih.gov/), a database created and managed by NIH’s National Library of Medicine.
The National Institute of Mental Health (NIMH) and the National Human Genome Research Institute (NHGRI) will co-administer the network on behalf of NIH. Program funding will transition out of the Roadmap in years five and six.
"Discoveries from genomics and proteomics have given us thousands of new proteins but little understanding of what many of them do in the cell," said Thomas R. Insel, M.D., NIMH director. "This screening effort will identify small molecules that influence these newly discovered proteins, allowing us to understand how many of them function. And for proteins involved in disease states, today’s small molecule could be tomorrow’s medication."
"This collaborative effort will give academic and government researchers in the global research community robust chemical tools to understand the cellular mechanisms of disease and a much more vigorous way to identify useful biological targets," said NHGRI Acting Director, Alan E. Guttmacher, M.D.
The nine institutions funded as part of the network are:
The Burnham Center for Chemical Genomics, La Jolla; Broad Institute Comprehensive Screening Center, Cambridge; National Institutes of Health Chemical Genomics Center, Bethesda;
The Comprehensive Center for Chemical Probe Discovery and Optimization at Scripps.
Specialized Screening Centers:
Johns Hopkins Ion Channel Center, Baltimore; Southern Research Specialized Biocontainment Screening Center, Birmingham; University of New Mexico Center for Molecular Discovery, Albuquerque
Specialized Chemistry Centers:
University of Kansas Specialized Chemistry Center, Lawrence; The Vanderbilt Specialized Chemistry Center for Accelerated Probe Development, Nashville.
In a new study in cells, University of Illinois researchers have adapted CRISPR gene-editing technology to cause the cell’s internal machinery to skip over a small portion of a gene when transcribing it into a template for protein building. This gives researchers a way not only to eliminate a mutated gene sequence, but to influence how the gene is expressed and regulated.