Protein engineering

One of the most compelling questions in receptor biology is whether, and how, the structural and chemical features of a receptor-ligand complex can qualitatively and/or quantitatively influence downstream signaling. That is, does extracellular structure matter ? or is intracellular signaling agnostic to the structural and geometric details of the extracellular engagement event ? Most transmembrane receptors we study, such as cytokine and growth factor receptors, are activated through some form of ligand-induced dimerization. This begs the question, will any dimer do ?

We are using protein engineering approaches, namely combinatorial biology methods such as yeast surface display to interrogate fundamental mechanistic questions about receptor signaling and molecular recognition. This involves a synergy with our structural targets to guide development of molecules with interesting signaling, functional and therapeutic properties. We are primarily integrating this approach into our studies of T cell receptor and cytokine receptor signaling.