Innate Immunity is the most ancient and evolutionarily conserved central defense system that distinguishes host-self from non-self microbial pathogens in plants, animals and humans. It provides the first line of inducible defense against infectious diseases and underlies the prevention of constant and omnipresent microbial invasion. A key function of innate immunity is the detection of microbe-associated molecular patterns (MAMPs), e.g., bacterial flagellin and fungal chitin, by pattern recognition receptors (PRRs) to launch appropriate defense responses. Recent discoveries have revealed remarkable convergent evolution in the recognition of diverse MAMPs by leucine- rich-repeat (LRR) receptors and the activation of multiple MAPK cascades in plants, animals and humans. Despite the universal and essential involvement of MAPK cascades in mediating MAMP signaling in plants, worms, flies, mammals and humans, the molecular mechanisms underlying the intertwined signaling webs remain mostly elusive due to the complexity of functional redundancy, mutant lethality and shared components in distinct signaling pathways. How the conserved immune responses are integrated with stress signaling sharing common regulators remains unclear. The goal of this research project is to establish a regulatory framework for the convergent MAMP and stress signaling mechanisms using Arabidopsis thaliana as a plant model system. The proposed experiments aim to integrate powerful functional genomic screens with comprehensive molecular, biochemical, cellular, genetic, genomic and chemical analyses to 1) discover new molecular links between the flagellin receptor (FLS2) complexes and MAPK cascades, 2) systematically elucidate the transcriptional network in dynamic and diverse plant defense responses, and to 3) uncover a previously unrecognized connection between TOR kinase signaling and innate immunity. Specifically, the project will focus on characterizing and integrating the newly discovered functions of RLCKs (receptor-like cytoplasmic kinases) in FLS2 signaling, flg22-triggered transcriptional networks modulated by key transcription activators and repressors, and novel TOR kinase substrates in stress and immune signaling. The project on uncovering the novel receptor-MAPK, calcium and TOR signaling mechanisms will establish new conceptual understanding in the regulation of immune responses and transcriptional networks beyond the plant system.
Aim 1. Analyze new functions of diverse RLCKs in FLS2-MAPKKK signaling complexes Aim 2. Dissect the dynamic transcriptional network in convergent MAMP signaling Aim 3. Explore novel TOR kinase substrates in connecting stress and immune signaling

Public Health Relevance

The versatile innate immune system underlies the ancient and evolutionarily conserved mechanisms for prevention of constant and omnipresent microbial invasion, and provides the first line of inducible defense against infectious diseases in plants, animals and humans. A key function of innate immunity is the detection of microbe-associated molecular patterns and danger signals to launch appropriate defense responses. The proposed research on pattern recognition receptor kinase signaling complexes, intertwined protein kinase cascades and transcriptional networks will discover novel and fundamental molecular mechanisms in immune and stress signaling, and provide innovative tools for future improvement of agriculture, environment and renewable energy production, as well as human health in treating infectious, inflammatory and autoimmune diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM070567-09
Application #
8630258
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Marino, Pamela
Project Start
2004-04-01
Project End
2017-12-31
Budget Start
2014-02-01
Budget End
2014-12-31
Support Year
9
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Li, Lei; Sheen, Jen (2016) Dynamic and diverse sugar signaling. Curr Opin Plant Biol 33:116-125
Cheng, Zhenyu; Li, Jian-Feng; Niu, Yajie et al. (2015) Pathogen-secreted proteases activate a novel plant immune pathway. Nature 521:213-6
Li, Jian-Feng; Zhang, Dandan; Sheen, Jen (2015) Targeted plant genome editing via the CRISPR/Cas9 technology. Methods Mol Biol 1284:239-55
Xiong, Yan; Sheen, Jen (2015) Novel links in the plant TOR kinase signaling network. Curr Opin Plant Biol 28:83-91
Hamel, Louis-Philippe; Sheen, Jen; S├ęguin, Armand (2014) Ancient signals: comparative genomics of green plant CDPKs. Trends Plant Sci 19:79-89
Zhou, Jinggeng; Wu, Shujing; Chen, Xin et al. (2014) The Pseudomonas syringae effector HopF2 suppresses Arabidopsis immunity by targeting BAK1. Plant J 77:235-45
Xiong, Yan; Sheen, Jen (2014) The role of target of rapamycin signaling networks in plant growth and metabolism. Plant Physiol 164:499-512
Li, Jian-Feng; Zhang, Dandan; Sheen, Jen (2014) Cas9-based genome editing in Arabidopsis and tobacco. Methods Enzymol 546:459-72
Sheen, Jen (2014) Master Regulators in Plant Glucose Signaling Networks. J Plant Biol 57:67-79
Li, Jian-Feng; Zhang, Dandan; Sheen, Jen (2014) Epitope-tagged protein-based artificial miRNA screens for optimized gene silencing in plants. Nat Protoc 9:939-49

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