Degron peptides: Cancer mutation hotspots and tools for synthetic biology

Degron peptides: Cancer mutation hotspots and tools for synthetic biology

Dr Andrew Wood; University of Edinburgh

Andrew did his PhD in the laboratory of Rebecca Oakey at Kings College London working on genomic imprinting. He was then awarded a Sir Henry Welcome Fellowship to work with Barbara Meyer at UC Berkeley, where he helped to develop the early genome editing technologies which paved the way for the CRISPR revolution. He started his own laboratory at the MRC Human Genetics Unit in 2014 with a Sir Henry Dale Fellowship and his current focus is on degrons, the peptide sequences that govern protein turnover kinetics. He leads a cluster in the MRC National Mouse Genetics Network focused on degron tags and their application in mouse models.

My laboratory develops genetic technologies to advance our understanding of human disease and therapeutics. This talk will cover two ongoing projects centred on the theme of protein degradation. First, I will discuss collaborative work using CRISPR saturating mutagenesis to quantify the effect of all possible missense mutations across the endogenous degron motif of ß-Catenin, which is one of the most frequently mutated regions in the genome of several human cancer types. We have integrated these mutational effect scores with clinical data to understand the relationship between mutational diversity, strength of oncogenic signalling, tumour – immune interactions and survival. Second, I will discuss our efforts to adapt synthetic degron tag technology for studying protein function and modelling protein degrader drug activity in mice, which we are undertaking as part of the MRC National Mouse Genetics Network.

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