Structural studies on ER-associated protein quality control mechanisms

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Quality control mechanisms are essential for clearing misfolded, non-functional proteins from the cell. This is especially important in the endoplasmic reticulum (ER) where secretory and cell surface proteins are synthesised. ER-associated degradation (ERAD) is an export pathway for misfolded proteins and comprises of various machinery for the selection, ubiquitination and extraction of membrane proteins from the ER. Its malfunction has been implicated in more than 60 human diseases, examples of which include Alzheimer's and cystic fibrosis. Mammalian ERAD mechanisms are still poorly understood and there has been minimal structural insight provided thus far. This project will take a multidisciplinary approach to characterise ERAD pathways in mammalian cells. Cryo-electron microscopy, biochemical and molecular analysis will be used to identify the molecular details of misfolded protein export.