Resistance pathway dynamics in plant immunity (Jane Parker)
Research in the Parker lab
We’re interested in understanding 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 defence pathways to turn on against a particular mode of pathogen infection and the need to respond to other competing environmental stresses. Using the model species Arabidopsis thaliana in association with biotrophic or hemi-biotrophic pathogens we’re working to identify key decision-making ‘nodes’ in pathogen recognition and resistance, to elucidate how such regulatory nodes connect to the cellular reprogramming machinery (through transcriptional and post-transcriptional processes) and to position disease resistance pathways within the broader environment sensing network. For this, we use forward and reverse genetic and genomic approaches. We also characterize functional protein complexes and dynamic protein-chromatin interactions in vivo, interpret protein crystal structures and structural models, perform live-cell imaging, and explore natural variation in stress network topologies within and between plant species.
If you’re interested in joining the group to pursue research any of the following areas, please contact Jane Parker (firstname.lastname@example.org) and our departmental secretary Simone Gieraths (email@example.com). We also highlight on our department web site a number of dates through the year for interviewing prospective PhD students or Postdocs.
Current Projects in the lab are:
We’re studying a large family of intracellular, multi-domain immune receptors (called TNLs) 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 defences 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.
In order 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. Our next steps 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.
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.
Here we aim to understand how the plant organizes and steers 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 current data suggest that, in ETI conferred by TNLs, the conserved EDS1-PAD4 defence regulatory node controls the fine-balance between different hormone pathways by interacting with and modulating the activities of various TFs and transcription repressors (TRs).
We have 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 has been a major step forward in characterizing functional EDS1 associations with TNLs on one side and with TFs/TRs on the other in plant immunity reprogramming. We have launched a crystal structure-guided mutational pipeline for EDS1 and PAD4 to identify key surface features and molecular rearrangements or modifications that couple EDS1 and its direct partners to gene expression outputs. Karsten Niefind and colleagues are crystallizing and performing SAXS analysis of new EDS1 protein conformational states to provide insights to the molecular organization of these important signalling modules.
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, together with Maria von Korff (Uni. Düsseldorf) and Armin Djamei (Gregor Mendel Institute, Vienna), generation of CRISPR/Cas9 knock-outs of EDS1 pathway orthologues in barley and Brachypodium to elucidate what we hypothesize will be a basic regulatory principle maintained across higher plant species.
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. On line.
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.
A lot of what we’ve learned about plant innate immunity (- the nuts and bolts of the system) has come from characterizing induced responses to homogenous and often non-physiological concentrations of a single microbial pathogen. An unanswered question is how relevant or penetrant these processes are in nature. Now that we’ve identified some of the key players in plant immunity and stress hormone signalling, we want to get a fuller insight to how the plant manages its biotic stress network under more natural conditions in which maintaining a balance between effective disease resistance and metabolic homeostasis is crucial for survival and growth. In nature, the plant integrates numerous environmental cues such as temperature, light, drought, herbivory, competition from other plants. Also, the plant hosts a structured population of benign and beneficial microorganisms inside its leaves and roots. These tertiary plant-microbe associations are likely to influence profoundly how a plant controls its defence system and responds to pathogen attack.
We’re approaching this broader question in two studies. First, we’re exploiting the phenomenon of immune-related hybrid incompatibility (HI) to locate naturally occurring allelic variants of immunity genes within Arabidopsis species that have been maintained in particular genetic accessions and cause temperature-conditioned immunity mis-regulation (auto-activation) when brought together in the same genotype by crossing. Immune-related HI likely reflects different evolutionary paths of immunity genes through genetic drift or selection. One HI combination of an intracellular receptor haplotype consisting of 8 TNL genes found in an Arabidopsis local population in Gorzów Wielkopolski, Poland, and particular allelic forms of a receptor-like kinase (SRF3) that have signatures of positive selection in central Asian accessions, has been studied intensively by Ruben Alcazar (now at Uni. Barcelona). Our aim is to use the Gorzów local population to ask whether the presence or absence of the TNL haplotype in genetically different individuals within a local population has a measurable effect on plant growth/survival and microbial associations in the field.
In the second study, we’re exploring the extent of natural variation, again within Arabidopsis species, in defence pathway homeostasis in response to two different ambient temperatures (20oC and 16oC). This analysis has uncovered extensive genetic variation in temperature-conditioned accumulation of the stress hormone SA, which correlates poorly with plant growth. Our initial results suggest a large degree of genetic plasticity in the regulation of defence outputs and maintaining growth. We’re now using a combination of GWAS and QTL analysis to identify candidate genes underlying the SA x temp trait variation. We’re also investigating whether differences in SA pathway homeostasis can be explained at the level of molecular cross-talk within the plant stress hormone network.
Alcazar R, von Reth M, Bautor J, Chae E, Weigel D, Koornneef M, Parker JE. 2014. Analysis of a plant complex resistance gene locus underlying immune-related hybrid incompatibility and its occurrence in nature. PloS Genet. 10, e1004848.
Gloggnitzer J, Akimcheva S, Srinivasan A, Kusenda B, Riehs N, Stampfl H, Bautor J, Dekrout B, Jonak C, Jiménez-Gómez J, Parker JE, Riha K. 2014. Nonsense-mediated mRNA decay modulates immune receptor levels to regulate plant antibacterial defense. Cell Host Microbe 16, 376-390.
Alcázar R and Parker JE. 2011. The impact of temperature on balancing immune responsiveness and growth in Arabidopsis. Trends Plant Sci. 16, 666-675.
Alcázar R, García AV, Kronholm I, de Meaux J, Koornneef M, Parker JE and Reymond M. 2010. Natural variation at Strubbelig Receptor Kinase 3 drives immune-triggered incompatibilities between A. thaliana accessions. Nature Genet. 42:1135-1139.
Alcázar R, Garcia AV, Parker JE and Reymond M. 2009. Incremental steps towards incompatibility revealed by Arabidopsis epistatic interactions modulating salicylic pathway activation. Proc. Natl. Acad. Sci. USA 106: 334-339.