Home Department: Biology
Mentor: Brian Kobilka (Molecular & Cellular Physiology)

"Probing Extracellular Domain Dynamics in Ligand Binding and Activation of the GLP-1 Receptor"

The glucagon-like peptide receptor (GLP-1R) is a therapeutic target for diabetes, affecting over 500 million people worldwide. GLP-1R agonists lower HbA1c by approximately 1%-1.5%, reflecting a sustained 25-40 mg/dL drop in blood glucose. Although prior studies indicate the extracellular domain (ECD) regulates ligand attachment, how ECD structural states propagate receptor activation remains poorly defined. The Kobilka lab uses glucagon receptor (GCGR) to probe ECD conformational dynamics via single-molecule fluorescence resonance energy transfer (smFRET), resolving state populations and transition kinetics to identify ECD states that couple ligand binding signaling and inform GLP-1R therapeutic design.