Chemical Biology Platform

Our chemists use modern organic synthesis in three phases of the platform's research. One team of chemists synthesizes a Broad Institute small-molecule screening collection. This team uses diversity-oriented synthesis to prepare compounds having the ability both to modulate nearly any aspect of human biology and to be optimized. The second team uses follow-up chemistry to optimize "hits" in small-molecule screens in order to develop small-molecule probes with high potency and specificity. The third team undertakes another significant and impacting challenge -- to convert "hits" to candidate small-molecule therapeutics, a key step in enabling human clinical investigations.

Our informatics team manages data collection and integration from chemical synthesis through screening and data analysis. Electronic lab notebooks and an analytical chemistry data warehouse capture critical information about the synthesis of compounds that are later used for screening. They also make these data available during the analysis of screening results. These tools facilitate a more comprehensive analysis of assay results that provides better biological understanding and leads to more informed decisions. Automated lab management systems enable high-throughput operation and improve data quality by eliminating error-prone manual processes. We make our data and analysis tools available to the global scientific community through the public database ChemBank.

Our small-molecule screening team, which has existed for over 10 years, has facilitated small-molecule screening projects for more than 140 different research groups throughout the U.S. and abroad. These scientists, in collaboration with automation engineers, have built and now operate unique automation systems for compound management and screening. These systems store and retrieve two unique small-molecule screening collections that together will comprise over 500,000 compounds. The facility provides the functionality and flexibility to perform a wide range of assays with extraordinary accuracy and production capacity. These assays include both target-based biochemical screens and cell-based phenotypic screens, using novel screening approaches (e.g., gene expression-based screening, high-content live-cell imaging, RNAi combined with small molecules) with relevance to disease areas including psychiatric disease, cancer, infectious disease, and diabetes.