Center for Network Systems Biology — Boston University

Target Discovery Lab

A specialized Fusion Eclipse Mass Spectrometer enables investigators on the Charles River Campus, and outside collaborators, to focus on determining the molecular targets of bioactive small molecules using innovative liquid chromatography mass spectrometry (LC/MS) techniques. The TDL advances research in chemical biology and moves into new, enriching territories for student and postdoctoral training across both campuses.

Running samples through the Exploris
Biological target identification (“target ID”) is a critical challenge in drug discovery which involves identification of the one (or few) proteins bound by a bioactive small molecule or drug among the many thousands in cells or tissues that are responsible for its biological effect(s). Target ID is essential for understanding a compound’s mechanism-of-action, and provides mechanistic insights into chemical probes, and facilitates regulatory approval and commercialization for therapeutic leads.
Since target ID remains a major unaddressed bottleneck for many research programs, Prof. Andrew Emili and John A. Porco, Jr. recently established the BU Target Discovery Laboratory. BU-TDL uses innovative compound-protein interaction mapping technologies based on unbiased precision mass spectrometry to monitor protein engagement by a ligand arising from a chemical screen or structural modeling to characterize structure-activity relationships (SAR i.e. pre-clinical efficacy).
Current assays include Cellular Thermal Shift Assay (CETSA), Target Identification by Ligand Stabilization/Thermal Profiling, Affinity Pulldown/Capture, and other unbiased chemical-proteomic methods that use precision LC/MS to obtain quantitative and qualitative information on the direct binding targets of bioactive compounds of interest from researchers in Chemistry, Biochemistry, Biology, Bioengineering, Medicine, or Pharma.
With support from the NIH (HEI 1S10OD026807 “Ultra-High Precision Mass Spectrometer”), the TDL recently acquired a state-of-the-art Orbitrap Fusion Eclipse Tribrid Mass Spectrometer (Fusion Eclipse), located at our new Charles River Campus (CRC) facility (LSEB #710) to advance this research, while enriching student and postdoctoral training. Using this instrumentation in combination with stable isotope labeling, we can measure ligand-induced protein stabilization in a systematic quantitative manner to identify the target(s) of bioactive compounds in different biological contexts.
Professor McComb in the lab
Graduate student Ethan at work
By achieving the highest possible accuracy, coverage, and throughput for target identification, the TDL is uniquely capable of documenting dose-responsive target engagement using multiplexing workflows that generate accurate and informative data.