Protein quality control
Dr John Christianson
My lab investigates how eukaryotic cells sense, respond to and resolve cellular stress through the mechanisms of protein quality control that ensure proteome fidelity. Cellular stress is a hallmark of cancer and many other diseases and the processes overseeing protein folding and degradation are essential for transformed cells to withstand adverse conditions. We have a long-standing interest in the protein quality control mechanisms at work in the endoplasmic reticulum (ER) and, specifically, the molecular machinery and substrates of ER-associated degradation (ERAD); a multifaceted process responsible for clearing misfolded and unwanted proteins from the ER through the ubiquitin-proteasome system.
We integrate proteomics, cell biology, functional genomics and biochemistry to identify essential ERAD factors, characterise functional complexes and understand how they enable cells to adapt to stress conditions associated with disease. Without stringent protein quality control mechanisms in the ER, cells cannot maintain homeostasis and do not survive under stress. Cancer cells commandeer these stress response pathways to support their survival and so our long-term goals involve identifying targets and developing pharmacological strategies that interfere with cancer progression by disrupting the protein quality control mechanisms required for stress adaptation.