Molecular Targets Program

The field of biomolecular screening technology has developed rapidly and in scientific sophistication during the past decade, driven by the advent of combinatorial chemistry, the broader availability of multiple sources of chemical diversity, the parallel evolution of genomics, and increasingly proteomics. Indeed, biomolecular screening "science" has emerged as a foundation discipline for molecular targets research, validation, drug discovery and development. There are now numerous journals, books and other publications, professional organizations and Internet sites providing abundant background information, as well as current approaches and ongoing developments in the field.

Often the rate-limiting phase of a discovery project is the development of a relevant, practical and valid assay model for primary screening of chemical diversity libraries. For primary screening, an ideal model must be amenable to incorporation into a high-throughput screening (HTS) platform. Another essential requirement is the development of complementary, secondary assays for evaluation and prioritization of primary screening hits.

Broadly, assay models for primary and/or secondary screening applications may encompass one or more of the following: receptor binding; immunoassay; enzyme assay; protein-protein interactions; protein-nucleic acid interactions; protein-carbohydrate interactions; gene expression; or functional assays. Detection methods typically encompass luminescent, fluorescent, or colorimetric endpoints. Assay models may be cell-based or biochemical, and may be homogeneous or heterogeneous. Cellular fluorescent imaging platforms are also under development within MTP.

The MTP invites CCR, NCI investigators to consider projects in which the unique knowledge, expertise, and research materials evolving from their intramural research can be utilized in collaboration with the MTP for the design, construction and use of novel biomolecular screening tools for molecular target validation, drug discovery and development.

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