Research in the Greene Lab

A sub-sample of human glutamine synthetase ensemble refinement models overlayed.

The Greene Lab’s research focuses on biochemistry, molecular biology, and structural biology, with an emphasis on understanding protein and enzyme function and regulation in human health and disease. This research platform serves as a training pipeline for students to learn cryo-electron microscopy (cryo-EM) data analysis and sample preparation. We apply this technique to the study of enzyme conformational heterogeneity and other macromolecular compelexes. Enzymes must undergo conformational changes to enhance enzymatic catalysis, and most enzymes form complexes that are available for structural determination by cryo-EM. Additionally, we study protein amyloids which are commonly found in disease states and have distinct shapes that cryo-EM is best at elucidated. Overall, the Greene lab aims to elucidate the fundamental principles of protein activity and regulation, as this basic knowledge contributes to potential therapeutic advancements.

Research topic

Image description

Ensemble-function analysis of human glutamine synthetase. We work in large teams to solve cryo-EM structures, perform MD ensemble refinement, and rationalize functional hypotheses for what conformations confer what features to the enzyme. We then experimentally test our hypotheses biochemically and with further structural models.