Policing secretion: protein quality control and traffic COPs

Research in the Miller lab is broadly aimed at understanding basic mechanisms of secretory protein biogenesis, focusing on protein quality control within the endoplasmic reticulum. They use the budding yeast, Saccharomyces cerevisiae, as a model system, which affords facile biochemical, genetic, genomic and proteomic tools. By using such a tractable model system, they can rapidly discover new pathways and dissect mechanisms that may be directly relevant to a number of human diseases, most notably cystic fibrosis and similar diseases of protein misfolding. Vesicle formation from the ER is relatively well understood and relies on cytoplasmic coat proteins known as the COPII coat. Yet, despite a relatively deep understanding of the mechanisms that drive COPII vesicle formation and cargo capture, we know very little about how this process is regulated to prevent improper traffic of misfolded proteins. One long-term goal is to understand how vesicle abundance and architecture can adapt to changing physiological needs with respect to cargo load.