Protein folding homeostasis - from mechanisms to interventions

How our cells respond to stress affects the outcome of physiological and pathological processes. Notable amongst these are the diseases of ageing, which sum-up life's stresses and our response to them. The biochemical processes our cells use to respond to stress have been honed by natural selection, and in aggregate have made us the successful, long-lived species that we are. However, peering into the details has taught us that the outcome of certain pathological processes may be improved by tweaking our responses to stress; strengthening some and weakening others. This proposal is predicated on that premise. Focusing on the response to protein misfolding in the secretory compartment of cells (a phenomenon known as endoplasmic reticulum stress), we aim to distinguish between adaptive and maladaptive responses. Using this information, we hope to create chemical tools to reset these responses, tools that may serve as the basis for therapy in the future.