Projects

Broad Institute Probe Development Center (BIPDeC)

in

Part of the Molecular Libraries Probe Production Center Network (MLPCN), the Broad Institute’s Probe Development Center (BIPDeC) was established in 2008 in order to discover and develop small-molecule probes and is sponsored by the NIH Road Map's Molecular Library Initiative. The Center engages in ~25 small-molecule probe development projects each year, which entails assay development, HTS, and follow-up chemistry and biology. All facets of the research are made available on the public databases PubChem and ChemBank. In addition to professional staff, Organic Synthesis Fellows, trainees with advanced training in organic synthesis, participate in this research effort.

The Center also manages a Center-Driven Research Project named “Genomic signature-based screening in robust HTS formats”. Here, we seek to develop general and robust HTS methods that enable the discovery of small molecules that switch, for example, disease states to healthy states without requiring knowledge of the relevant cellular target(s) in advance of the screen. These methods require the ability to perform multiple measurements per well that together define signatures of the relevant states, for example, by measuring the relative amounts of tens or hundreds of mRNAs, miRNAs, phosphoproteins, or by imaging similar numbers of subtle features of cells. Even in their current pilot phase, these methods have already yielded small-molecule probes and clinical candidates that would not have been discovered otherwise. Gene expression- and image-based signature screening will first be advanced from their current pilot stage to a mature HTS stage.

We will also develop nascent yet promising methods that yield alternative signatures of cell states based on, for example, chromatin marks or cellular metabolites, and tools for the comparative analysis of signature-based, multidimensional HTS datasets. We will make these capabilities and tools available to the MLPCN and larger scientific community.

Further Information

  • Process for BIPDeC endorsement of NIH R03/X01 and R21 applications