Over the past decades, growing evidence has highlighted remarkable similarities between the innate immune systems of the plant and animal kingdoms. These ‘shared’ innate immune systems include intracellular receptors as exemplified by nucleotide-binding leucine-rich repeat proteins (NLRs). Our group aims to unravel the underlying mechanistic parallels between plant and animal immune components using plants as a model. Our research programme encompasses a diverse array of experimental systems including genetics, genomics and cellular and structural biology with an emphasis on immunity and cell death.
Current Research Programme
Many proteins involved in cell death execution or cell death-associated immunity in plants, animals and fungi are characterised by the presence of a four-helical bundle structure named the HeLo domain after the fungal HET and LOPB proteins. One salient example of a HeLo domain-containing protein is MLKL (mixed lineage kinase domain-like protein), which mediates necroptosis in vertebrates.
We recently discovered a conserved protein family across seed plants that structurally and functionally resembles the animal necroptosis mediator MLKL. The Arabidopsis thaliana genome encodes three MLKLs (AtMLKLs) with overlapping functions in disease resistance mediated by Toll-interleukin 1-receptor domain intracellular immune receptors (TNLs). AtMLKLs contain an N-terminal helical bundle, termed the HeLo domain, which confers cell death activity, yet is dispensable for AtMLKL-dependent immunity. Based on the current understanding of the mode of action of animal MLKL, we hypothesise that animal and plant MLKLs share a common mechanism defined by oligomerisation and translocation to the plasma membrane, ultimately leading to plasma membrane damage, cell death and immunity. However, the molecular mechanisms of how plant and animal MLKL induce cell death remains unknown. We aim to understand the molecular principles of MLKL-mediated cell death and immunity by determining and comparing the nanoscale organization and cellular dynamics of this protein family in plant and animal cells.