iTKP fusions: Structure, function and engineering of an emerging plant disease resistance system

Context and Challenge: Yield from key crops that feed the world is threatened by abiotic and biotic stresses. Pre-harvest plant disease can decimate crop production by small-holder farmers and is estimated to reduce yields by 20-30% in modern agriculture despite the intensive interventions used (e.g. pesticides). However, current chemical control of pathogens is not sustainable due to the direct impact of their use on the environment and the environmental and economic cost of production. There’s a pressing need to reduce chemical control of plant diseases within the background of the climate emergency and emergence of pathogens in new areas. The overarching aim of this proposal is to develop new genetic solutions for managing blast disease, caused by the fungus Magnaporthe oryzae, in cereal crops. With collaborators, we have discovered novel components of the plant immune system that could deliver new solutions to managing plant diseases, but first we need to understand how they work, and then how they can be engineered. In time, our discoveries should be applicable to managing other plant diseases. Like animals, plants have an immune system that helps defend against disease. This immune system includes receptors, proteins that detect pathogens and pests, and activate immune responses. Frequently, immune receptors from inside plant cells (intracellular receptors) detect “effector” proteins, pathogen-derived molecules delivered to promote disease. Pathogens are often adapted to particular plant hosts, and plant/pathogen co-evolution has led to a diverse set of immune receptors encoded in different plant genomes. Most research in the last ~30 years has focussed on one type of intracellular immune receptor (called NLRs). Recently though, a new type of receptor (the tandem kinase proteins or TKPs) is being repeatedly found using modern approaches to disease resistance discovery. Aims and Objectives: There is an urgent need for broadening the genetic basis of plant disease resistance and understanding how we can help plants fight back against disease. This project will address this challenge by integrating extensive preliminary data and expertise in the Banfield Lab, along with collaborators, to address the following specific objectives: Demonstrate that binding determines immune activation by validating crystal structures of effector/receptor domain complexes using in vitro and in vivo assays. Establish the diversity of interactions available to drive immune engineering by profiling an interaction matrix of iTKP-HMA (receptor) domains and effectors from M. oryzae and other pathogens. Explore the molecular mechanism of iTKP signalling, specifically in the context of integrated HMA domains. Develop and test iTKPs as chassis for engineering immune responses to pathogen effectors. Potential applications and benefits: Plant immune receptors are deployed in breeding programs to genetically encode resistance, protecting crop harvests from disease. But due to pathogen co-evolution with plants, new disease management resources are continually required. Here, by understanding how a new family of receptors works and can be engineered we will boost plant immunity, providing new avenues towards more sustainable agriculture. The research fits BBSRC's priorities for “sustainable agriculture and food” as detailed in the Strategic Delivery Plan 2022-2025, addressing a crucial global challenge. It also fits the current responsive mode spotlight area of “Plant Health - Development of novel crop protection strategies”.