The mechanisms and physiology of ER-associated protein degradation

All cells in our body are highly compartmentalised by small membrane-bound structures or ‘organelles’, each with a unique identity and a specialised set of functions. The endoplasmic reticulum (ER) is the largest of these organelles and it carries out several essential functions, including the production of cell surface and secreted proteins through which cells communicate with their environment and the lipids used to build cellular membranes and store energy. In addition, the ER assembles the ‘nuclear envelope’, a membrane that wraps around DNA and keeps it away from other cellular events.

We will investigate how these different functions depend on a process that degrades ER proteins because they are abnormal, they are no longer needed or they are present in the wrong place. Accumulation of these unwanted proteins in the ER has dire consequences to cellular physiology and might result in diseases such as atherosclerosis and cancer. We will examine how they are selected from the thousands of proteins of the ER, which signals are involved and how they are decoded.