Hundreds of thousands of molecules, collected and purified from natural sources or synthesized by chemists around the world, will be tested against biological targets for inhibitory or activating activity. The Penn center is one of nine facilities that the NIH is establishing across the country as part of the Molecular Library Screening Center Network.
"This initiative is comparable in scale and complexity to the Human Genome Project," said Scott Diamond, professor of chemical and biomolecular engineering and director of the new center. "Small molecules come in an astronomically large variety of shapes and sizes that dwarfs the number of genes in the human genome. Finding the important ones within the NIH repository is a classic needle-haystack challenge, but we have robotic and biosensing tools that weren't available even a decade ago."
Each of the new NIH centers will be screening the compound repository against unique targets of biological interest provided by scientists around the country. The screening centers will create a massive, public-domain database where the interactions of thousands of chemicals with scores of biological targets can be data-mined. Such tools have previously been available to university researchers only in a very limited way at few sites.
"I can envision scientists around the world who study a disease or organism or a particular set of molecules downloading information that would have normally taken years to obtain," Diamond said.
The Penn center has developed a very special capability to print thousands of molecules on a glass surface the size of a business card and then test the molecules against proteases and other enzymes purified from human or animal cells, bacteria, parasites, insects or viruses. As targets for drug development, proteases have proven critical to viral infection or replication, cancer cell migration, inflammation and blood clotting.
"We can probe chemical-biological interactions in nanoliter volumes the size of a speck of dust," Diamond said.
Penn will also be able to test compounds in thousands of miniature wells each containing a millimeter-sized zebra fish, an unlikely organism that has proven its worth in studies of heart or nerve function as well as in cancer biology because the transparent fish is easily imaged.
When the researchers identify a new molecule that reacts to a specific target, the results will be added to a database open to the public. Using the "hits" of the chemical screening, Amos Smith, a professor in Penn's Department of Chemistry, will head the effort to create highly tailored, higher potency molecules useful in biological research, imaging and pharmacological research.
"In time, these exciting new molecules with known biological activities will be a mouse-click away for chemists, biologists and drug designers to use, all supported by an extensive database," Smith said. "This is really an exciting time for chemistry at the interface with biology."
The Penn Center for Molecular Discovery will be housed at the Institute for Medicine and Engineering. The center represents a truly multidisciplinary exercise, involving engineers with skills in robotics from Penn's School of Engineering and Applied Sciences, chemists from Penn's School of Arts and Sciences and biomedical researchers from Penn's School of Medicine.
"The integration across Penn's campus is enhanced by its connectivity with the other centers in the national network," Diamond said. "This could have a stimulating effect on the pace of discovery by opening information up to anyone that might have a great idea."
For more information, visit: http://www.seas.upenn.edu/~pcmd/