Plant pathogenic microbes cause significant economic damage to global food crop production systems. Pathogens are specialised microbes that manipulate the host defense circuitry to suppress immunity and promote virulence. Interestingly, many of the processes that determine immunity or susceptible interactions, take place in the host nucleus. With the identification of vast repertoires of (nuclear) secreted pathogen proteins (effectors) and host signaling components that extert their functions in the nucleus, this host compartment is now considered an important interface where outcomes are decided.This proposal aims to unravel the molecular mechanisms that underpin infection outcomes in the nucleus. A powerfull approach that will combine quantitative proteomics with gene expression analyses will be used to (i) detect pathogen effectors in the host nucleus in situ and (ii) identify changes in the nuclear proteome during infection. I will then use Yeast two Hybrid and immunoprecipitation to identify effector host targets before placing these components in a nuclear immune signalling context. New information on effector-induced changes in the host nuclear proteome coupled to immune signalling, will then be used to rationalise implementation of two synthetic approaches towards resistance.I will design synthetic (non)host targets that are immune to effector induced modifications and function towards immunity. In addition, identification of key effectors and targets will be used to design new R-gene like specificities, embodied in synthetic Nucleotide-Binding Leucine Rich Repeat proteins (sNB-LRR). Overall, this work will impact studies on host-microbe interactions and importantly, will provide proof of concept for two new synthetic breeding strategies in plants.