SYNOPSIS, MOLECULAR LIBRARY TRANSITION PLANS 2007

The Molecular Libraries and Imaging (MLI) Program was the first Roadmap project to go through the midcourse review process. Following the midcourse review, the MLI Implementation Group (MLIIG) presented a plan for the program to transition from the pilot phase to the production phase. Discussion with the IC directors, Dr. Krensky (OPASI Director), Dr. Kington (NIH Deputy Director) and Dr. Zerhouni (NIH Director) ensued and the following plan was put into place.

It was agreed that the purpose of the program is to create a resource that the community finds useful and that has a major impact on the way biomedical research is done by increasing the understanding and application of chemical genomics.

In the production phase, the MLI will be focused on more difficult problems and provide novel resources for research investigators. First, it will encourage the development and screening of less traditional assays utilizing novel methods on new targets for the purpose of advancing the understanding of molecular and cellular biology. Greater emphasis will be placed on phenotypic assays for which the target activity may not be known. In addition, it will increase the chemistry capacity of the network, allowing academic researchers to develop more useful probes from initial hits. Second, it will invite each center to develop innovative proposals to attack difficult or unique problems in chemical genomics. To reach these aims, it will reduce the number of comprehensive centers from 10 to 3 or 4 and fund additional but smaller, complementary centers focused on chemistry or on screening more specialized, lower throughput assays, for example phenotypic assays.

To increase synergy within the network, changes will be made in several initiatives. The cheminformatics efforts will be refocused to more closely complement the efforts of the centers and a workshop will be held to address the need for bioinformatics tools to mine chemical biology data in PubChem. The chemical diversity of the compound library will continue to be enhanced in the Small Molecular Repository through de novo library synthesis initiatives and by acquisition of previously characterized, diverse libraries. Libraries synthesized will be deposited in the Small Molecule Repository and instrumentation developed within the MLI will be tested in the centers when feasible.

Processes will be implemented to more closely estimate and follow the probability of success of each screening project. The MLIIG project team will work with assay providers and the centers to plan, monitor, and redirect or end each project. Several new RFAs incorporating these improvements have been issued.

To reassess the MLI and chart the overall direction at the 5-year point, an ongoing assessment will be made of the program with the close cooperation of the MLIIG program staff and OPASI program and evaluation staff. This assessment will inform a midcourse review to occur midway through the production phase as well as the transition from Roadmap funding, slated to begin in 2012.