Grant: Project Grant

Targeted protein degradation (TPD) is one of the most promising innovations in drug discovery. While most traditional small molecules inhibit the function of a therapeutically relevant target protein, in TPD, the targed protein is degraded. This has several advantages over inhibition, such as increased drug potency and specificity. In TPD, a target protein is brought to close proximity of another protein called E3 ligase that can degrade the target. However, although the human genome encodes over 600 E3 ligases, only very few of them have been harnessed for TPD. We recently developed a novel method to identify, in an unbiased manner, proteins that could be harnessed for targeted protein degradation. We discovered many E3 ligases that are more potent than currently used E3s in TPD. Moreover, we identified many proteins that do not look like typical E3 ligases or other proteins involved in degradation. In this project, we will use large-scale screens to characterize how these unconventional proteis function in protein degradation and investigate whether they could be used for targeted protein degradation therapeutics.