Understanding how plants perceive environmental challenges and process the signals to generate adaptive responses is a central goal of plant research to improve crop yields under numerous abiotic or biotic stresses.  I hope to address aspects of this problem by elucidating versatile roles of the mitogen-activated protein kinase (MAPK) cascade in stress, immunity, growth, and development. The MAPK cascade represents the most universal and essential signaling module from plants to humans. In Arabidopsis, among the 20 members of the MPK family (the last tier of the cascade), MPK4 and MPK3/6 govern a wide range of cellular programs in stress and immune responses as well as in growth and development. Studies with genetic mpk mutants where kinase activity is non-existent from the zygote stage, possess experimental limitations or offer contradictory findings that are difficult to explain. For example, mpk4 is severely dwarfed from the cytokinesis defect and abnormal activation of immunity, and the mpk3mpk6 double mutant is lethal in early embryogenesis (Fig. 1a). Therefore, our knowledge about definitive and precise roles of MAPKs in specific signaling pathways has been limited for the last two decades. 

Advances in structure-guided design of ATP analogs have provided the potency and selectivity of chemical inhibitors to dissect protein kinase signaling pathways. During my research as a postdoctoral fellow and as an assistant faculty member, I established a versatile and robust plant platform to deconvolute the complexity and multifaceted functions of the core MAPKs as central signaling hubs. The engineered MAPK system where in vivo MAPK activity can be immediately inhibited by administering the ATP analog 3MBiP, provides a powerful tool to dissect specific signaling pathways at any developmental stage. (Fig 1b-e). By integrating chemical genetics, genomics, network and systems analyses, I determined 1) the distinctive profiles of combinatorial MAPK activation dynamics and MAPK target transcriptomes for diverse stimuli, 2) the core MAPK network responsible for shared stress and immune responses, 3) genome-wide MPK4 and MPK3/6 target genes in six categories of primary immune transcriptional programs, and 4) dynamic interplay between MPK4 and MPK3/6 in the regulation of primary immunity. Furthermore, by systematically calibrating 3MBiP concentrations and examining the time- and dose-based perturbations of in vivo MAPK activity, I discovered the precise range of threshold activities for both MPK4 and MPK3/6 in regulating six different cellular programs (Fig 1f and 1g). The findings provide biological and mechanistic explanations for how MPK4 differentially modulate signal-triggered immunity, autoimmunity as well as cytokinesis; and how MPK3/6 distinguish immunity, shoot epidermal cell patterning, and stem-cell reprogramming in the root meristem.

Numerous new findings from my previous and current research will serve as a platform for the future research as an independent principal investigator in department of Plant Biochemistry of Ghent University Global Campus. My long-term research goal is to understand fundamental molecular mechanisms in stimuli sensing and signaling that regulates growth and adaptation to stress in plants, and to develop practical means to advance plant biotechnology and improve crop productivity in agriculture.  My short-term research plans are 1) to further elucidate the molecular mechanisms in microbe-associated molecular patterns (MAMP)-MAPK signal transduction in plants and identify novel factors associated with MAPK activity to enhance plant immunity, and 2) to understand fundamental mechanisms of plant post-embryonic development by dissecting signaling processes for stem cell regulation and cell type patterning governed by MPK3/6 and, cytokinesis by MPK4. To achieve these goals, I will take full advantage of chemical genetics approach integrated with a classic genetic approach, cutting-edge techniques of genomics, cell biology, biochemistry, and systems biology.