Resistance pathway dynamics in plant immunity

Research in the Parker lab

We’re interested in how plants activate and fine-tune their innate immune responses. Plants react rapidly and effectively against attacking pathogens and are able to gauge exquisitely which resistance pathways to turn on to combat a particular mode of pathogen infection, as well as the need to respond to competing environmental stresses such as drought or competition from other plants. Using the model species Arabidopsis thaliana in association with biotrophic or hemi-biotrophic pathogens we’re working to identify decision-making ‘nodes’ in pathogen recognition and resistance, to elucidate how these regulatory nodes connect to the cellular reprogramming machinery (through transcriptional and post-transcriptional processes), and to position disease resistance pathways within the broader environmental sensing network.

We apply forward and reverse genetic and genomic approaches in well-known A. thaliana genetic lines and exploit natural variation within the species. We’re also extending our analyses of stress network properties to a temperate monocot crop, barley. To elucidate key molecular processes and interactions in immunity, we’re characterizing nuclear receptor and resistance signalling protein complexes and changes in protein-chromatin associations during transcriptional activation of particular defence sectors. Central to our progress in this area is the analysis of protein crystal structures and structure-guided design of protein variants, live-cell imaging and FRET-FLIM analyses, ChIP-seq, RNA-seq, LC-MS/MS mass-spectrometry, bioinformatics and computational phylogenetic studies of protein evolutionary covariation.

If you’re interested in joining the group to pursue research in the following broad areas, please contact Jane Parker () and our departmental secretary Jutta Weinand () with a CV and a short description of your research interest.

Current Projects in the lab are:

1. Host intracellular pathogen recognition and mobilization of resistance pathways

We’re studying a large family of intracellular, multi-domain immune receptors (TNL type NLRs) that has expanded and diversified in dicot species but, as far the genome data tell, has not persisted in monocot plant lineages. In Arabidopsis and other dicot species, TNL receptors become activated by pathogen virulence factors (called effectors) that interfere with basal defence pathways in different ways and in different parts of the cell. The activated TNL receptors transduce signals leading to dynamic nuclear reprogramming and transcriptional derepression of defence pathways through a rather conserved set of lipase-like proteins (EDS1, PAD4, SAG101) whose central component is EDS1. EDS1 has an essential nuclear function in pathogen resistance which can be uncoupled from host programmed cell death (pcd) that often accompanies effector-triggered immunity (ETI). EDS1 associations with several nuclear TNL receptors suggests it connects different TNLs molecularly to downstream defence pathways.

To piece together TNL receptor activation and early signalling events, we’ve focused on an Arabidopsis nuclear TNL pair, RRS1 and RPS4, which operates as a chromatin-bound heterodimer recognizing two structurally different bacterial effector molecules, Pseudomonas syringae AvrRps4 and the Ralstonia solanacearum YopJ family acetyl-transferase, PopP2. Recent analysis of RRS1/RPS4 complex activation led by Laurent Deslandes and colleagues at LIPM-CNRS/INRA (Toulouse) together with our group at MPIPZ shows that RRS1/RPS4 directly intercepts a broad sweep immune-suppressing activity of PopP2 targeting a family of defensive WRKY transcription factors (TFs). RRS1/RPS4 achieves this by integrating a WRKY DNA-binding ‘decoy’ domain within the RRS1 receptor protein. Fusions with NLR receptors of other domains potentially mimicking effector operational targets in different plant species suggests a fundamental mechanism for increasing receptor recognition ‘space’ as well as new avenues for engineering receptors that could effectively capture the disease-promoting activities of  important crop pathogens. Current experiments, together with the Deslandes group, are to measure changes in the nature of TNL/EDS1 complexes between pre- and post-activation states, on and off the chromatin. This will provide insights to mechanisms by which immune receptor sensing of pathogen interference is transduced to defence outputs in plant cells and tissues.

Selected publications:

Le Roux C, Huet G, Jauneau A, Camborde L, Trémousaygue D, Kraut A, Zhou B, Levaillant M, Adachi H, Yoshioka H, Rafaele S, Berthomé R, Couté Y, Parker JE and Deslandes L. 2015. A receptor pair with an integrated decoy converts pathogen disabling of transcription factors to immunity. Cell, 161, 1074-1088.

Cui H, Tsuda K, Parker JE. 2015. Effector-triggered immunity: from pathogen perception to robust defense. Annu. Rev. Plant Biol. 66, 487-511.

Griebel T, Maekawa T and Parker JE. 2014. Nucleotide-binding oligomerization domain-like receptor cooperativity in effector-triggered immunity. Trends Immunol. 35, 562-570.

Williams SJ, Hoon Sohn K, Wan L, Bernoux M, Sarris P, Segonzac C, Ve T, Ma Y, Saucet SB, Ericsson DJ, Casey LW, Lonhienne T, Winzor DJ, Zhang X, Coerdt A, Parker JE, Dodds PN, Kobe B and Jones JD. 2014. Structural Basis for Assembly and Function of a Heterodimeric Plant Immune Receptor. Science 344, 299-303.

Heidrich K, Tsuda K, Blanvillain-Baufumé S, Wirthmueller L, Bautor J and Parker JE. 2013. Arabidopsis TNL-WRKY domain receptor RRS1 contributes to temperature conditioned RPS4 auto-immunity. Frontiers Plant Sci. 4: Article 403.

Zbierzak AM, Porfirova S, Griebel T, Melzer M, Parker JE and Dörmann P. 2013. A TIR-NBS protein encoded by Arabidopsis Chilling Sensitive 1 ( CHS1) limits chloroplast damage and cell death at low temperature. Plant J. 75:539-552.

Heidrich K, Blanvillain-Baufumé S and Parker JE. 2012. Molecular and spatial constraints on NB-LRR receptor signaling. Curr. Opin. Plant Biol. 15: 385-391.

Heidrich K, Wirthmueller L, Tasset C, Pouzet C, Deslandes L and Parker JE. 2011. Arabidopsis EDS1 connects pathogen effector recognition to cell compartment-specific immune responses. Science, 334: 1401-1404.

Garcia AV, Blanvillain-Baufumé S, Huibers RP, Wiermer M, Li G, Gobbato E, Rietz S and Parker JE. 2010. Balanced nuclear and cytoplasmic activities of EDS1 are required for a complete plant innate immune response. PLoS Pathogens 6: e1000970.

Birker D, Heidrich K, Takahara H, Narusaka M, Deslandes L, Narusaka Y, Reymond M, Parker JE and O’Connell R. 2009. A locus conferring resistance to Colletotrichum higginsianum is shared by four geographically distinct Arabidopsis accessions. Plant J. 60: 602-613.

Wirthmüller L, Zhang Y, Jones JD and Parker JE. 2007. Nuclear accumulation of the Arabidopsis immune receptor RPS4 is necessary for triggering EDS1-dependent defence. Curr. Biol. 17: 2023-2029.

2. Steering the plant stress hormone network in effector-triggered immunity

Here we aim to understand how the plant organizes and directs its defence network towards particular resistance outputs as a crucially important element of the plant immune response. In induced resistance against biotrophic pathogens this involves the boosting of salicylic acid (SA)-related defence pathways and dampening of conflicting hormone systems, such as those controlled by jasmonic acid/ethylene (JA/ET) which are important against necrotrophic pathogens, or abscisic acid (ABA), a key abiotic stress hormone. Our data suggest that, in ETI conferred by TNLs, the conserved EDS1-PAD4 defence regulatory node controls the fine-balance between SA and JA/ET pathways by interacting with and modulating the activities of a set of TFs and transcription repressors (TRs). We recently established that a core function of EDS1 with PAD4 in Arabidopsis is to protect the SA-regulated defence sector against genetic and pathogen perturbations.

We determined the crystal structure of an EDS1-SAG101 heterodimer in collaboration with the group of Karsten Niefind at The Institute of Biochemistry (Uni. Cologne), and from that deduced a structural model of the EDS1-PAD4 heterodimer complex. This offers a major step forward for characterizing functional EDS1/PAD4 associations with TNLs on one side and with TFs/TRs on the other, in immunity reprogramming.  We have launched a crystal structure-guided mutational pipeline for EDS1 and PAD4 to identify key surface patches and molecular rearrangements or modifications that couple EDS1 and its direct partners to TFs/TRs and gene expression regulation. Karsten Niefind and colleagues are crystallizing and performing SAXS analysis of new EDS1 protein conformational states to provide further clues to the molecular dynamics of this resistance signalling module.

Complementing the above work, we’ve initiated a study with the computational network modeling groups of Andreas Beyer (CECAD, Uni. Cologne) and David Ochoa (EMBL-European Bioinformatics Group, Hinxton, UK) to construct a co-evolutionary framework around EDS1. This should enable us to identify co-evolving nuclear protein modules and help to pin-point biologically meaningful conserved and diversifying features of the EDS1 signalling node across dicot and monocot plant lineages. This study goes alongside a deep phylogenetic analysis of EDS1 family protein domains across seed plant lineages and generation of CRISPR/Cas9 knock-outs of EDS1 pathway orthologues in barley to elucidate what we hypothesize will be a basic regulatory principle maintained across higher plant species.

Selected publications:

Cui H, Gobbato E, Kracher B, Qiu J, Bautor J, Parker JE. 2017. A core function of EDS1 with PAD4 is to protect the salicylic acid defense sector in Arabidopsis immunity. New Phytol. 213: 1802-1817.

Makandar R, Nalam VJ, Chowdhury Z, Sarowar S, Klossner G, Lee H, Burdan D, Trick HN, Gobbato E, Parker JE and Shah J. 2015. The combined action of ENHANCED DISEASE SUSCEPTIBILITY1, PHYTOALEXIN DEFICIENT4 and SENESCENCE-ASSOCIATED GENE101 promotes salicylic acid-mediated defences to limit Fusarium graminearum infection in Arabidopsis thaliana. Mol. Plant-Microbe Interact. 28: 943-953.

Wagner S, Stuttmann J, Rietz S, Guerois R, Brunstein E, Bautor J, Niefind K and Parke, JE. 2013. Structural Basis for Signaling by Exclusive EDS1 Heteromeric Complexes with SAG101 or PAD4 in Plant Innate Immunity. Cell Host Microbe, 14:619-630.

Kim T-H, Kunz H-H, Bhattacharjee S, Hauser F, Park J, Engineer C, Liu A, Ha T, Parker JE, Gassmann W and Schroeder JI. 2012. Natural variation in small molecule-induced TIR-NB-LRR signaling induces root growth arrest via EDS1- and PAD4-complexed R protein VICTR in Arabidopsis. Plant Cell 24: 5177-5192.

Louis J, Gobbato E, Mondal HA, Feys BJ, Parker J. and Shah J. 2012. Discrimination of Arabidopsis PAD4 activities in defense against green peach aphid and pathogens. Plant Physiol. 158: 1860-1872.

Kim T-H, Hauser F, Ha T, Xue S, Böhmer M, Nishimura N, Munemasa S, Hubbard K, Peine N, Lee B, Lee S, Robert N, Parker JE and Schröder JI. 2011. Chemical genetics reveals negative regulation of abscisic acid signaling by a plant immune response pathway. Curr Biol. 21:990-997.

Rietz S, Stamm A, Malonek S, Wagner S, Becker D, Medina-Escobar N, Vlot AC, Feys BJ, Niefind K, and Parker JE. 2011. Different roles of EDS1 bound to and dissociated from PAD4 in Arabidopsis immunity. New Phytol. 191:107-119.

Bartsch M, Bednarek P, Vivancos PD, Schneider B, von Roepenack-Lahaye E, Foyer CH, Kombrink E, Scheel D and Parker JE. 2010. Accumulation of isochorismate-derived 2,3-dihidroxybenzoic 3-O-β-D-xyloside in Arabidopsis resistance to pathogens and ageing of leaves. J. Biol. Chem. 285: 25654-25665.

Straus MR, Rietz S, ver Loren van Themat E, Bartsch M and Parker JE. 2010. Salicylic acid antagonism of EDS1-driven cell death is important for Arabidopsis immune and oxidative stress responses. Plant J. 62: 628-640.

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