Abstract

Friday 13 February, 13:00 – 14:00

Speaker: Professor David Ron

Talk Title: How is Endoplasmic Reticulum Stress Recognised?

Biography: David studies the adaptation of eukaryotic cells to the burden of unfolded proteins in their endoplasmic reticulum (ER). The context for this research is the observation that cells have mechanisms to ensure proper folding of proteins, but failures to maintain the proteome lead to toxic effects known as ‘proteotoxicity’. The latter affects poorly renewable tissues of long-lived organisms, exerting its deleterious consequences over extended periods of time. The accumulative erosive effects of proteotoxicity are believed to contribute to numerous diseases of ageing.

To meet this challenge, eukaryotes have evolved signalling pathways that detect the level of mismatch between burden and capacity (resulting in ER stress) and elicit rectifying responses. Collectively this constitutes an unfolded protein response (UPR) and is the focus of our lab.

Their long-term goal is to contribute to a detailed molecular understanding of protein folding homeostasis in the ER and to exploit this insight to develop tools for manipulating the UPR and possible therapies for inevitable failures of homeostasis. In this vein, our most important accomplishments of recent years are the elucidation of the biochemical basis of UPR activation and the discovery of a stress-responsive enzymatic mechanism that matches ER chaperone activity to unfolded protein burden post-translationally.