James Olzmann

2017 Hellman Fellow

olzmann@berkeley.edu

Assistant Professor, Nutritional Science & Toxicology
UC Berkeley

Project title: Global identification of endogenous ERAD substrates

Proteins in our cells are subject to stringent molecular oversight to ensure correct protein folding, localization, and function. Proteins failing to achieve their native conformation are detected by protein quality control systems that refold the protein, prevent protein aggregation, and/or target the protein for degradation. Mutations in protein quality control machinery or age-related declines in cellular quality control capacity cause numerous human diseases. Often termed “conformational” disorders, this large class of diseases includes neurodegenerative diseases, metabolic disorders, liver diseases, systemic amyloidosis, and many others.

The research project funded by the Hellman Fellowship will explore the mechanisms that mediate protein degradation in the endoplasmic reticulum (ER), a cellular folding compartment that functions as the port of entry into the secretory pathway. Not only does the ER have robust protein quality control systems, but it also has important protein quantity control systems that regulate critical cellular process such as cholesterol biosynthesis. Our research utilizes a novel substrate trapping method to identify proteins that are degraded by the ER-associated degradation (ERAD) pathway. The results from these studies will advance our understanding of the mechanisms that underlie protein recognition and degradation by ER protein quality and quantity control systems.