INSPIRE · System-wide discovery and analysis of inositol pyrophosphate signaling networks in plants

Inositol pyrophosphates (PP-InsPs) are soluble signaling molecules known to play diverse roles in fungal and animal cell signaling. The metabolism of PP-InsPs in plants however is poorly understood and many signaling pathways controlled by PP-InsPs remain to be discovered. Funded by an ERC starting grant, we have previously identified protein sensor domains for PP-InsPs, which allow PP-InsPs to act as central regulators of phosphate homeostasis in all eukaryotes. Genetic disruption of PP-InsP synthesis results in dramatic phenotypes in the model plant Arabidopsis, which however cannot be rationalized by defects in phosphate signaling only. Based on these physiological observations, we generated a system-wide Arabidopsis PP-InsP interactome, using an affinity-matrix absorbed non-hydrolyzable PP-InsP analog. Surprisingly, hundreds of novel candidates from different protein families were identified in this screen, now enabling us to study PP-InsP catabolism and a multitude of PP-InsP-mediated signaling processes. Here, I propose to combine quantitative biochemistry and structural biology with cell biology and genome editing to dissect plant PP-InsP signaling networks at the physiological level and in mechanistic detail. Specifically, we will define the roles for PP-InsPs in plant light sensing and signaling, in flowering time regulation and in plant immune responses. Our ultimate goal will be to investigate the cross-talk between different PP-InsP-controlled signaling pathways and to define central signaling hubs. I envision that the work outlined in this proposal will yield a mechanistically validated system’s-level view of PP-InsP signal transduction in plants, which may allow us to better understand how plants develop and interact with their environment, and that may enable us to improve crop performance in the future.