Pathogen effector recognition by MLA immune receptors and reconstitution of receptor-mediated cell death in animal cells
Supervision: The project will be supervised by Paul Schulze-Lefert at the Max Planck Institute for Plant Breeding Research.
Abstract: Plants have evolved an innate immune system to protect themselves from pathogenic microbes. One arm of this immune system relies on intracellular immune sensors, which are encoded by disease resistance genes and trigger potent immune responses when non-self molecules are detected. These cytoplasmic proteins are typically nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and structurally related to innate immune sensors in animals, including humans. Most plant NLRs are categorized into three groups: the sensor coiled-coil (CC) domain-containing NLRs (CC-type NLRs or CNLs), sensor Toll-Interleukin-1 receptor (TIR) domain NLRs (TIR-type NLRs or TNLs), and signaling (helper) HeLo (HET-S and LOPB)-like domain-containing NLRs. NLRs are able to detect the presence of pathogen-derived avirulence effectors (AVRs) whose function is to aid the infection process of pathogens. Plant accession-dependent and pathogen strain-specific NLR-AVR interactions lead to effector-triggered immunity (ETI), often associated with localized host cell death, the hypersensitive response (HR), which is thought to eliminate nutrient supply to invading pathogens. Characterized AVRs of the fungal pathogen Blumeria graminis f. sp. hordei (Bgh) are directly recognized by barley NLR receptors (MLA) encoded at the polymorphic mildew locus a (Mla). The first aim of this project is to identify a Bgh AVRA effector and the cognate MLA3 receptor that is known to confer dual disease resistance to Bgh and the fungal pathogen Magnaporthe oryzae, the causal agent of rice blast. Heterologous expression of matching barley MLA and Bgh AVRA effectors is necessary and sufficient to trigger a cell death response in Nicotiana benthamiana and Arabidopsis thaliana. In an extension of these experiments, we will test whether activated CC-type MLA receptors can function autonomously to cause cell death through their expression in human HEKT cells to investigate the existence of common or distinctive cell death mechanisms activated by plant and animal/human NLR receptors.
Link to the Schulze-Lefert group homepage: https://www.mpipz.mpg.de/schulze-lefert