Improving plant immunity by synthetic exploitation of the ubiquitin system (SynUbL)

Improving plant immunity by synthetic exploitation of the ubiquitin system (SynUbL)

Plants are continuously attacked by pathogens and pests, resulting globally in large agricultural losses and food insecurity at high economic cost. To counter infection, plants have developed sophisticated immune responses in which the post-translational modifier, ubiquitin, plays indispensable roles. Ubiquitination is a versatile protein modification that regulates the amplitude and intensity of immune responses, thereby establishing durable resistance. Substrate ubiquitination is performed by E3 ligases that act as matchmakers by recruiting specific substrates. Despite the essential roles of E3 ligases in plant immunity, it remains unclear how they achieve such extraordinary substrate selectivity and how they evolved to adapt to changing threats in their environment, including new pathogens. Conversely, pathogens have evolved effector proteins that hijack ubiquitin signalling to prevent immune activation, but the underpinning molecular mechanisms remain obscure.

The SynUbL project will establish interactions between the major cereal crop, barley, and fungal pathogen, Puccinia hordei, as an economically relevant host-pathogen system for addressing these questions and to bioengineer durable resistance. By functionally tracking immune-induced E3 ligases along the evolutionary tree, we will reveal how these enzymes evolved structural features for specific substrate recognition. Simultaneously, we will expose P. hordei’s hijacking tactics, thereby uncovering the significance of ubiquitin in shaping the evolutionary arms race between host and pathogen. Collective insights are then utilised to synthetically engineer novel E3 ligases to allow on-demand activation of host immune pathways and on-demand destruction of immune-suppressing pathogen effectors. Hence, this project not only provides fundamental discoveries in ubiquitin signalling, it exploits these innovations by generating sustainable strategies for durable crop resistance in the agrifood sector.