Speaker: Sam Bevill, Qi Lab
Talk Title: Engineering tumor-specific PROTACs in MDM2-amplified cancers

Description: High-level amplification of the MDM2 oncogene is a common mechanism for inactivating P53’s tumor suppressive functions in cancer. Unfortunately, efficacy of conventional MDM2 inhibitors is compromised by on-target toxicity and feedback loops that drive exceptionally high MDM2 levels. We present a PROTAC-based strategy that harnesses excess MDM2 to selectively target MDM2-amplified tumor cells while sparing normal cells.


Speaker: Hanjie Jiang, Cole Lab
Talk Title: Protein semisynthesis reveals plasticity in HECT E3 ubiquitin ligase mechanisms

Description: Lysine ubiquitination, catalysed by E3 ubiquitin ligases, is pivotal for regulating protein stability and cell signalling. Using protein semisynthesis, the roles of the C-terminal carboxylate and conformational interconversion in HECT-domain E3 catalysis are now characterized, revealing evolutionary plasticity in side chain versus backbone utilization.