As part of NIH's Roadmap, which has as its overarching theme "New Pathways to Discovery," NIH has allocated $88.9 million over the next three years to create the Molecular Libraries Screening Centers Network (MLSCN). NIH selected nine outside institutions as pilot centers to be included in the network, as well as NIH's Chemical Genomics Center. Each center will work to develop the necessary tools conducting so-called high throughput screenings of molecules – which by the third year will allow each center to screen up to 100,000 molecule compounds using 20 different approaches, or assays, that help determine how these compounds interact with molecular targets, within cells, and are involved in regulating events that may be the root cause of different diseases.
Pitt's center takes advantage of close ties between the School of Medicine's Department of Pharmacology and the School of Arts and Sciences' Department of Chemistry, along with new facilities devoted to drug discovery in the newly constructed Biomedical Science Tower-3. It also represents a unique collaboration with neighboring Carnegie Mellon University and Sandia National Laboratories in Albuquerque, N.M., and provides the UP-MLSC unique expertise in design and development of novel probes that use fluorescence and other optical imaging techniques.
"As a pilot center in the Molecular Libraries Screening Centers Network, we will be able to exploit and expand our existing strengths for developing and implementing methods for the detection, characterization and refinement of small molecules that have attractive biological and pharmacological properties and may eventually be further developed as therapeutic approaches to treating various diseases and conditions," said John S. Lazo, Ph.D., the Allegheny Foundation Professor of Pharmacology at the University of Pittsburgh School of Medicine and principal investigator of the UP-MLSC.
Pitt's center was selected because of the unique expertise of its investigators, including Dr. Lazo, who will direct a core devoted to assay implementation; Andreas Vogt, Ph.D., research assistant professor of pharmacology in Pitt's School of Medicine, will focus on high throughput screening, which will exploit Pitt's existing expertise in screening compounds in the context of whole cells. Peter Wipf, Ph.D., University Professor in the Department of Chemistry, School of Arts and Sciences, and co-principal investigator, will lead the synthetic chemistry core. The focus of that core will be to further improve and refine compounds designated as being the most promising to better target the specific errors that occur on the smallest of scales yet have profound effects on the development of disease. Mark D. Rintoul, Ph.D., manager of computational biology at Sandia National Laboratories, will direct the informatics core.
An NIH steering committee for the MLSCN, of which Dr. Lazo will be a member, will determine which of the most promising methods for screening molecules will be pursued and select from among its network of funded pilot centers those that will develop and implement these particular assays.
All information collected on assays and high throughput screenings of compounds will be included in NIH's new database, PubChem, to ensure that resources developed from the MLSCN will be made available to the scientific community.