Biology subjects

Deichmann, M.

Publications and source records attributed to Deichmann, M..

5 recordsLinked to original sources

bioRxiv2024

M1-linked Ubiquitination by LUBAC Regulates AMPK Activity and the Response to Energetic Stress

Methionine-1 (M1)-linked ubiquitin chains, assembled by the ubiquitin ligase LUBAC and cleaved by the deubiquitinase OTULIN, are critical regulators of inflammation and immune homeostasis. Genetic loss of either LUBAC or OTULIN causes autoinflammatory syndromes, which are associated with defects in glycogen and lipid metabolism. However, how LUBAC and OTULIN regulate metabolic signalling remains unknown. Here, we demonstrate that LUBAC promotes, while OTULIN restricts, activation of the key metabolic regulator AMP-activated protein kinase (AMPK) in cells, mice, and human samples. LUBAC and OTULIN interact with AMPK, control its M1-ubiquitination, and regulate its activation in response to glucose starvation and allosteric activation. During starvation, LUBAC deficiency impairs autophagy induction and hinders the shift from oxidative phosphorylation to glycolysis. Strikingly, LUBAC-deficient Drosophila have a strongly reduced survival rate after starvation. Our work identifies LUBAC and OTULIN as physiological regulators of AMPK, providing the first mechanism by which M1-linked ubiquitin chains regulate metabolic signalling.

cell biology↗

bioRxiv2024

A synthetic platform for multiplex screening of cell-cell communication between soil fungi

Fungi are essential members across ecosystems, yet phytopathogenic fungi pose an increasing risk to crop yields. Despite their ecologic importance, cell-cell communication in fungi is underexplored, partly due to the lack of high-throughput techniques. Here we developed a Yeast Mating Platform (YeMaP) to investigate the interaction between fungal G protein-coupled receptors (GPCRs) and pheromone peptides. We used YeMaP for high- throughput screening of 8,000 pheromone sequences and identified new peptides with improved agonism or antagonism action. We found that these peptides can be applied in a native fungal system such as the plant pathogen Fusarium oxysporum, to control hyphal chemotropism and reduce plant root penetration. Additionally, we utilized YeMaP in a one- pot assay to investigate how abiotic factors influence the communication of multiple pheromone-GPCR combinations and found that the cell-cell communication mediated by the GPCR Ste2 from F. oxysporum signalled robustly across different abiotic factors, while other fungal GPCR-pheromone interactions were more sensitive to changes. Taken together, YeMaP accelerates the identification of fungal GPCR-peptide interactions by enabling one- pot assays, and serves as model system for studying fungal cell-cell communication.

synthetic biology↗

bioRxiv2023

Engineered yeast cells simulating CD19+ cancers to control CAR T cell activation

Chimeric antigen receptor (CAR) T cells have become an established immunotherapy and show promising results for the treatment of hematological cancers. However, modulation of surface levels of the targeted antigen in cancer cells affects the quality and safety of CAR T cell therapy. Here we present the Synthetic Cellular Advanced Signal Adapter (SCASA) system, based on successful engineering of yeast to simulate cancer cells with tunable surface-antigen densities, as a tool for controlled activation of CAR T cell responses and assessment of antigen density effects. Specifically, we demonstrate I) controllable antigen-densities of CD19 on yeast using G protein-coupled receptors (GPCRs), II) a customizable system allowing choice of signal input and modular pathway engineering for precise fine-tuning of the output, III) synthetic cell-cell communication with CAR T cells and the application of CD19-displaying yeast in the characterization of CAR designs, and IV) more efficient and robust activational control of clinically-derived CAR T cells in comparison to the NALM6 cancer cell line. Based on this yeast-based antigen-presenting cell system, we envision efficient assessment of how varying antigen densities in cancer cells affect CAR T cell responses and ultimately support development of safer and better quality of personalized cancer therapies.

synthetic biology↗

bioRxiv2023

Heritable maize microbiomes contribute to local adaptation and host stress resilience

Beneficial interactions with microorganisms are pivotal for crop performance and resilience. However, it remains unclear how heritable the microbiome is with respect to the host plant genotype and to what extent host genetic mechanisms can modulate plant-microbe interactions in the face of environmental stress. Here, we surveyed the root and rhizosphere microbiome of 129 accessions of locally adapted Zea mays, sourced from diverse habitats and grown under control and different stress conditions. We quantified treatment and host genotype effects on the microbiome. Plant genotype and source environment were predictive of microbiome composition. Genome wide association analysis identified host genetic variants linked to both rhizosphere microbiome composition and source environment. We identified transposon insertions in a candidate gene linked to both the abundance of a keystone microbe Massilia and source total soil nitrogen, finding mutant plants to show a reduction in lateral root density. We conclude that locally adapted maize varieties exert patterns of genetic control on their root and rhizosphere microbiomes that follow variation in their home environments, consistent with a role in tolerance to prevailing stress.

genetics↗

bioRxiv2022

Engineered cell differentiation and sexual reproduction in probiotic and mating yeasts

G protein-coupled receptors (GPCRs) enable cells to sense environmental cues and are indispensable for coordinating vital processes including quorum sensing, proliferation, and sexual reproduction. GPCRs comprise the largest class of cell surface receptors in eukaryotes, and for more than three decades the pheromone-induced mating pathway in bakers yeast Saccharomyces cerevisiae has served as a model for studying heterologous GPCRs (hGPCRs). Here we report transcriptome profiles following mating pathway activation in native and hGPCR-signaling yeast, and use a model-guided approach to correlate gene expression to morphological changes. From this we demonstrate mating between haploid cells armed with hGPCRs and endogenous biosynthesis of their cognate ligands. Furthermore, we devise a ligand-free screening strategy for hGPCR compatibility with the yeast mating pathway and enable hGPCR-signaling in the probiotic yeast Saccharomyces boulardii. Combined, our findings enable new means to study mating, hGPCR-signaling, and cell-cell communication in a model eukaryote and yeast probiotics. One-sentence summaryEnabling sensing in probiotic yeast and synthetic yeast mating with human and fungal G protein-coupled receptors.

cell biology↗