"Degrons: Cancer mutation hotspots and tools for synthetic biology"

Host: Professor Alessio Ciulli

Venue: CeTPD Seminar Room

Abstract 

Degrons are motifs within proteins that determine degradation rates. This talk will cover two projects which highlight the importance of natural degrons in cancer, and synthetic degrons for chemical genetic protein control. First, I will discuss collaborative work which used saturation genome editing to dissect the consequence of all possible missense mutations in the endogenous degron of ß-Catenin, which is one of the most frequently mutated regions in the genome of several human cancer types. This revealed a gradient of effects on canonical wnt pathway activation resulting from different cancer mutations, and activation strength could be used to predict the extent of immune cell infiltration in hepatocellular carcinoma patients. Second, I will discuss our efforts to adapt synthetic degron tag technology for studying protein function and modelling protein degrader drug activity in mouse models, which we are undertaking as part of the MRC National Mouse Genetics Network. We have generated mice expressing a single synthetic biosensor protein that can be degraded via dTAG, BromoTag, and AID2 ligands. This has enabled us to evaluate each system in living tissues, and to obtain insights on degrader drug pharmacology. 

This seminar is fully funded by external sources

ALL WELCOME