The Jefferson Group seeks to understand how conformationally dynamic protein complexes influence signaling across the cell membrane and exploit this for the design of receptors and signaling components with altered functions. Membrane proteins are constantly exposed to interactions with other proteins, whether it be oligomeric associations within the lipid bilayer, activation by peptide ligands, or coupling to downstream signaling effectors. These associations are critical hubs for cellular programming, and thus play key roles in disease states in which undesirable complex formation can trigger adverse consequences, such as protein misfolding, cell signaling defects, and activation of carcinogenic transcriptional programs.

As such, protein signaling complexes are uniquely poised for engineering efforts to correct such defects or grant new cellular functions, however, the rational design of membrane protein complexes has been hampered by the dearth of high-resolution structural models and experimental dynamics data. The Jefferson Group develops new methods for modeling conformational dynamism to both uncover the molecular determinants of membrane protein stability and function, as well as engineer new protein-based therapeutic and synthetic biology tools.