Environmental stresses continuously challenge protein homeostasis (proteostasis) and threaten cellular function by promoting the accumulation of damaged or misfolded proteins. We propose that this proteotoxicity represents a common molecular consequence of both biotic and abiotic stress and is a major determinant of plant performance. Our research aims to understand how plants maintain proteostasis under stress and how these mechanisms can be engineered to generate more resilient crops. We view proteostasis as an integrated regulatory network in which protein synthesis, intracellular trafficking, and protein degradation function as three highly interconnected processes that collectively determine cellular homeostasis. Rather than acting independently, these pathways continuously communicate to regulate protein abundance, quality, localization, and activity during stress.

Our research focuses on four interconnected themes.

Stress-induced regulation of protein synthesis. We investigate how pathogens and environmental cues reprogram translation through RNA metabolism and biomolecular condensates such as processing bodies. By understanding how protein synthesis is selectively controlled during stress, we aim to reveal the earliest mechanisms by which plants adapt while minimizing proteotoxic damage (González-Fuente et al., 2026 PMID 42030395)

Spatial organization of proteostasis. Our recent single-cell RNA sequencing studies demonstrate that proteostasis is organized in a highly cell-type-specific manner. Different tissues deploy distinct protein quality-control pathways that together coordinate immunity and stress adaptation across the whole plant. We seek to understand how translation, trafficking, and degradation are integrated within individual cell types and how communication between tissues orchestrates systemic resilience (Zhu et al., 2026, bioRxiv 2026.04.06.716646).

Proteostasis regulators and protein quality control. We study the molecular mechanisms that maintain protein homeostasis through endoplasmic reticulum quality control, intracellular trafficking, the ubiquitin-proteasome system, selective autophagy, and organelle communication. A major goal is to identify the regulatory nodes that coordinate these pathways and determine how they are manipulated during stress (Langin et al., 2026 PMID 42066754).

Ultimately, our research establishes proteostasis as a unifying framework for understanding plant stress biology. By linking molecular mechanisms across scales—from individual proteins and organelles to single cells, tissues, and whole plants—we seek to uncover general principles of proteostasis regulation and translate these discoveries into innovative strategies for engineering stress-resilient crops.

The interplay between endomembranes and autophagy

Proteomic analysis of possible targets of pathogen-induced autophagy led to the discovery that in addition to the proteasome, other pathways such as RNA metabolism, protein translation and vesicle trafficking might be autophagy targets or regulators. Based on this preliminary data we have identified a vesicle trafficking component as a novel modulator of autophagy (Gouguet et al., unpublished). It appears that the loss of this and other trafficking components and interference with protein secretion at ER exit sites modulates autophagy responses revealing a novel layer of crosstalk between the endomembrane system and autophagy mechanism.

Bacterial effector proteins as probes to dissect cellular degradation pathways

Using Pseudomonas and Xanthomonas effectors we have systematically screened them for their ability to interfere with proteasome function and autophagy. IP-MS experiments with candidate effector proteins revealed a subset of effectors interacting with autophagy components. So far, we have identified a Xanthomonas effector that is able to target an autophagy component to modulate autophagic turnover (Leong et al., in preparation), which we will further characterize using cell biological and biochemical approaches. We will extend our studies to other effector proteins and are  currently using the CRISPR/Cas9 technology to engineer tomato plants with altered proteolytic profiles.

Specificity of proteasome regulation during plant immunity

Regulatory fine-tuning of the proteasome is central to the outcome of plant-microbe interactions and seems to be a sensitive combination between down- and up-regulation of its activity. Therefore, we are currently analysing the mechanistic insights of how the proteasome is regulated on the transcriptional and post-translational level during plant immunity in a project funded through the CRC1101. Within this project we have identified two transcription factors that regulate proteasome gene expression during bacterial infection (Langin et al., unpublished). Interaction studies with both transcription factors revealed various proteins implicated in their degradation via the ERAD system and trafficking to the nucleus from the ER. Currently, we are looking into additional target genes of these transcription factors as they seem to mediate the trade-off between proteasome activation, growth and defence.

To protect themselves from these pathogens, plant immunity is efficiently regulated at the transcriptional and post-transcriptional level. The compartmentalization of mRNA into translationally repressed aggregates called processing bodies (PBs) is a key post-transcriptional regulatory process involved in development and stress responses. Preliminary results have shown that the bacterial plant pathogen Pseudomonas syringae (Pst) induces the formation of PB upon infection in an effector-dependent manner and that PB-defective Arabidopsis plants are more tolerant to Pst. This suggests that PBs are negative regulators of plant immunity that can be targeted by the bacterial effectors. The proposed project aims precisely at studying the role of PBs as post-transcriptional regulators of plant immunity and the ability of Pst effectors to modulate them. For this, a combination of genetic, biochemical, proteomic and cell biology approaches will be conducted to address: 1) the dynamics and roles of PBs, 2) the effector-mediated modulation of PB formation and 3) the interplay between PBs and autophagy, all in the context of a compatible plant-bacterium interaction.

In a more complete scenario, plants are constantly exposed to different pathogenic and beneficial microbes and hence it is crucial to include the bacteriome (microbiome) into this equation to obtain a holistic picture of the role of autophagy in plant-microbe interactions. The picture is getting even more complex if we look at cell-type specific autophagy response on the plant side. By studying how the microbiome and how different cell-types might shape autophagy and vice versa, we will get a deeper understanding of the role of autophagy in plant-microbe interactions. Thus, we will study in the ERC Starting Grant funded project DIVERSIPHAGY following questions and objectives:

• How does the bacteriome impact autophagy and vice versa?
• Can we use the bacteriome to identify the autophagy degradome and novel autophagy factors?
• Do bacteria shape tissue and cell-type specific modulation of autophagy?

In DIVERSIPHAGY, we will use a combination of state-of-the-art biochemical, proteomic, single-cell transcriptomics and cell-type specific reverse genetic approaches to decipher the role of autophagy in plant-microbe interactions. We aim to obtain a holistic view of how autophagy plays a role in plant-microbe interactions utilizing bacterial, genetic and cellular diversity with an emphasis on cell-type and organ-specific autophagy responses.