Organic Chemistry Seminar
Biological systems are inherently heterogeneous, both at the molecular level (e.g., encoded proteins existing in distinct posttranslational modification states) and the cellular level (e.g., organization of biomolecules to distinct regions of a cell or distinct cells within a tissue). To understand regulatory mechanisms in these systems under normal or diseased states, we must be able to probe biomolecular function in native environments across scales of space and time. Existing proteomic platforms provide quantitative snapshots of the proteins present in a biological sample, yet these methods typically require homogenization of samples, signal-averaging over thousands-to-millions of cells, and provide no information on protein function. Therefore, innovation in the development chemical probes and technology platforms is needed to study protein function and participation in signaling networks within complex native environments. In the first part of this talk I will describe the development of new chemical probes and complementary proteomic platforms enabling quantitative proteomic measurements in native biological contexts – ranging from sub-cellular complexes, single cells, primary tissues to live animals. In the second half of this talk I will describe how integration of these platforms can be harnessed to discover new roles for endogenous metabolites as intracellular signals in normal and diseased biological states, as well as the potential to regulate these signals for therapeutic benefit. Both halves of the talk will emphasize these integrated chemical proteomic platforms as a discovery engine to identify novel targets for diagnostic and therapeutic development in human disease.