We are building a group of chemists, physicists, biologists, and engineers at Johns Hopkins University to investigate the principles of signal transduction, the process by which chemical information is integrated in living systems. In cells, signal transduction relies on a complex network of biochemical reactions properly orchestrated in space and time. Signaling reactions at the cell membrane present a fascinating architecture of this complexity, where the presence of membrane surfaces confers unique mechanisms that are rarely seen in solution biochemistry. We take a highly interdisciplinary, quantitative approach to resolve the complexity of signal transduction, always with a strong physical perspective. We build reconstituted systems to control the complexity, design imaging assays to characterize the complexity, and develop kinetic models to understand the complexity—and from all of which, we aim to understand the fundamental principles governing biochemical reactions in living systems.

Examples:
12_3

 

 

 

 

 

Movie 1 Reconstituted protein condensates (labeled) on membranes.
Movie 2 Kinetic bifurcation of single-molecule kinetics (yellow) driven by condensates.
Movie 3 Single-molecule activation assay on membranes. The microarray allows the unambiguous assignment of enzymatic turnover (red) to a single recruitment event (yellow).

Selected references: Science 2019; PNAS 2016; PNAS 2021; PNAS 2024; Nat. Commun. 2022.