Tailored immune receptor engineering for resistance against rice blast disease

Fungal pathogens are a major constraint to crop production worldwide. As part of their virulence strategy, pathogens secrete effectorproteins to manipulate host machinery and promote colonization. Effectors can be recognized by host immune receptors that launcha robust immune response that restricts pathogen spread. Pathogens quickly overcome immune receptor-mediated resistance bymodifying or losing effectors to evade detection. In the Tailored Immunity project, our aim is to massively expand the effectorrecognition specificity of immune receptors to provide durable disease resistance against the fungus Magnaportha oryzae, the causalagent of blast disease, and one of the most destructive diseases of rice. In order to do this, we will use a host-target guidedengineering approach to replace the heavy-metal associated (HMA) effector binding domain of nucleotide-binding and leucine-richrepeat domain (NLR) immune receptors from rice with the HMA domain of host proteins that are targeted by multiple M. oryzaeeffectors. We hypothesize that introducing the HMA domain of the newly identified effector hubs to NLRs will allow the simultaneousrecognition of numerous effectors. As the pathogen would need to undergo complex mutation pathways to escape this detection,and since changing multiple effectors is presumably associated with high fitness costs, we expect that this new strategy will generateresistance that the pathogen has difficulties to overcome and that is therefore highly durable. By these means, this ambitious project promises to provide a proof-of-concept for a new knowledge-guided and powerful approach for the creation of durable immune receptors that will be highly valuable for the improvement of a large range of crop species. In addition to boosting host immunity, the Tailored Immunity project will provide invaluable information about how immune receptors can be engineered for tailored disease resistance in crops.