We study how biological systems sense, transmit, and organize information across scales. Single-molecule biophysics, quantitative imaging, protein engineering, and cell biology let us connect the dynamics of individual molecules to the behavior of cells.
At the plasma membrane, receptors convert chemical and mechanical inputs into biochemical output. We resolve those conformational transitions one molecule at a time, which tells us how drugs activate, inhibit, and bias signaling, and gives us what we need to design new proteins that control receptors on our own terms.
Inside the cell, information also has to be organized in space. Proteins and nucleic acids condense into membraneless compartments that cells assemble, dissolve, and partition on a schedule, and we ask what physical principles make that process reliable and reproducible.
How receptors turn signals into action
Cells sense their environment through membrane receptors that convert chemical and mechanical inputs into intracellular signals. We study how these inputs reshape receptor conformations and how those structural changes control downstream signaling.
Our work combines single-molecule FRET, chemical biology, site-specific labeling, and quantitative biophysics to follow receptor motions directly and resolve states that are hidden in ensemble measurements. A major focus has been class C GPCRs, which play central roles in synaptic transmission and have been a long-standing system of our lab for uncovering principles of receptor activation, allostery, and drug action.
Adhesion GPCRs offer a unique and still enigmatic mechanism for converting mechanical and extracellular cues into intracellular signals through their unusually large extracellular domains. We study how their built-in agonist is controlled, how forces and extracellular ligands reshape receptor conformation, and how these motions are translated into signaling. Our work combines single-molecule FRET with biochemical and functional measurements in cells.
