Protein biosynthesis is complex. To function properly, new proteins must be accurately synthesized from mRNA, fold into specific three-dimensional structures, undergo posttranslational modifications, assemble into multi-component complexes, and localize to the correct cellular destination. Each step of protein biosynthesis is closely monitored by regulatory and quality control processes that are essential for maintaining cellular homeostasis and preventing various human diseases. We aim to dissect the molecular mechanisms that determine the fate of nascent proteins using strategies that incorporate biochemistry, cell biology, and structural biology.
Our approaches include:
- Reconstituting protein biosynthesis and quality control processes using cell culture, in vitro lysate-based, and completely purified experimental systems.
- Developing methods and generating reagents to identify, uncouple, and mechanistically dissect the individual steps and molecular components of these cellular pathways.
- Isolating or assembling biologically-relevant macromolecular complexes that represent functional intermediates of these pathways for structural analysis, primarily via single-particle electron cryomicroscopy (cryo-EM).