Biology subjects

Bjornson, M.

Publications and source records attributed to Bjornson, M..

6 recordsLinked to original sources

bioRxiv2025

Antigen-scaffolds drive preferential expansion of functional genetically engineered CAR and TCR T cells

The engineering of autologous T cells to express chimeric antigen receptors (CARs) can induce profound clinical responses in haematological malignancies, while T cell receptor-engineered T (TCR T) cells have led to durable responses in clinical trials for solid tumours. However, clinical manufacturing of engineered T cells is resource-intensive and often yields highly differentiated, exhausted effector T cells. To circumvent this, we have developed an antigen-scaffold (Ag-scaffold) technology to preferentially expand genetically engineered T cells. Such Ag-scaffolds present cognate antigen together with stimulatory factors such as cytokines. By providing a specific and receptor-engaging stimulation to CAR/TCR T cells, the expanded product is highly enriched for engineered T cells with a favourable proliferative and efficacious phenotype. We expanded TCR T cells with Ag-scaffolds presenting peptide MHC (pMHC), and anti-CD19 CAR T cells with Ag-scaffolds presenting CD19 antigen. By applying cognate pMHC Ag-scaffolds, we achieved >80% antigen-specific T cells (83.62%{+/-}9.2%) after 14 days of culture with a distinct cytotoxic, proliferative phenotypical profile. Ag-scaffold expansion enhanced initial TCR and CAR cytotoxicity; sustained control was observed after repeated rechallenges of CAR T cells. In vivo, Ag-scaffold-expanded CRISPR/Cas9-engineered anti-CD19 CAR T also showed complete tumour eradication in a B-cell lymphoma xenograft model with a low dose of CAR T cells, which was not achieved using IL2/7/15 expansion.

immunology↗

bioRxiv2025

Genome-Wide Discovery and Characterization of Terpene Synthases Contributing to Strawberry Aroma Metabolism

Strawberry (Fragaria X ananassa) is a globally cultivated fruit crop valued for its unique flavor and aroma. Major groups of volatile organic compounds that contribute to strawberry aroma include terpenes, fatty acid esters, furanones, and benzenoids. Understanding the biosynthetic genes and pathways underlying strawberry terpene metabolism provides resources for developing precision breeding strategies to improve strawberry aroma traits. Here we describe the genome-wide identification and functional analysis of the terpene synthase (TPS) family that governs terpene chemical diversity in strawberries. Mining of the allo-octoploid genome of the cultivar Royal Royce identified 75 TPS gene candidates. Biochemical characterization of 27 predicted mono-, sesqui- and di-TPS enzymes via in vitro activity assays and in vivo enzyme co-expression studies demonstrated a range of TPS activities that are relevant for the biosynthesis of two thirds of known strawberry terpenes as well as products not previously described in octoploid strawberry. Complementary metabolomic and transcriptomic studies across a diversity panel of strawberry accessions demonstrated substantial variation in the composition and abundance of more than 30 detected accession-specific and common terpene aromas, nine of which matching characterized TPS products. Analysis of a developmental time series of two accessions with contrasting aroma further revealed accession-specific alterations of terpene metabolism during fruit ripening. These results expand our understanding of strawberry aroma metabolism and characterized terpene aroma genes as a resource for the molecular breeding of desirable aroma traits. One-sentence summaryDiscovery and characterization of the terpene synthase family that controls the diversity of terpene aroma metabolism in accessions of strawberry. Significance StatementThe diverse class of terpenoids contributes to complex crop traits, including plant growth, stress resilience, pollination, nutrition, and aroma. The discovery of terpene-biosynthetic pathways in octoploid strawberry (Fragaria X ananassa) provides foundational knowledge of the diversity of terpenoid metabolism in this important specialty crop toward applications in improving aroma traits.

plant biology↗

bioRxiv2023

Cutin-Derived Oligomers Act as Damage-Associated Molecular Patterns in Arabidopsis thaliana

The cuticle constitutes the outermost defensive barrier of most land plants. It comprises a polymeric matrix - cutin, surrounded by soluble waxes. Moreover, the cuticle constitutes the first line of defense against pathogen invasion, while also protecting the plant from many abiotic stresses. Aliphatic monomers in cutin have been suggested to act as immune elicitors in plants. This study analyses the potential of tomato cutin oligomers to act as damage-associated molecular patterns (DAMPs) able to induce a rapid immune response in the model plant Arabidopsis. Cutin oligomeric mixtures led to Ca2+ influx and MAPK activation in Arabidopsis. Comparable responses were measured for cutin, which was also able to induce a reactive oxygen species (ROS) burst. Furthermore, treatment of Arabidopsis with cutin oligomers resulted in a unique transcriptional reprogramming profile, having many archetypal features of pattern-triggered immunity (PTI). Targeted spectroscopic and spectrometric analyses of the cutin oligomers suggest that the elicitors compounds consist mostly of two up to three 10,16-dihydroxyhexadecanoic acid monomers linked together through ester bonds. This study demonstrates that cutin breakdown products can act as DAMPs; a novel class of elicitors deserving further characterization.

plant biology↗

bioRxiv2021

Perception of a conserved family of plant signalling peptides by the receptor kinase HSL3

Plant genomes encode hundreds of secreted peptides; however, relatively few have been characterised. We report here an uncharacterised, stress-induced family of plant signalling peptides, which we call CTNIPs. Based on the role of the common co-receptor BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1) in CTNIP-induced responses, we identified the orphan receptor kinase HAESA-LIKE 3 (HSL3) as the CTNIP receptor via a proteomics approach. CTNIP binding, ligand-triggered complex formation with BAK1, and induced downstream responses all involve HSL3. Notably, the HSL3-CTNIP signalling module is evolutionarily ancient, predating the divergence of extant angiosperms. The identification of this signalling module will help establish its physiological role and provides a resource to understand further receptor-ligand co-evolution.

plant biology↗

bioRxiv2021

ACTIVATION LOOP PHOSPHORYLATION OF A NON-RD RECEPTOR KINASE INITIATES PLANT INNATE IMMUNE SIGNALING

Receptor kinases (RKs) play fundamental roles in extracellular sensing to regulate development and stress responses across kingdoms. In plants, leucine-rich repeat receptor kinases (LRR-RKs) function primarily as peptide receptors that regulate myriad aspects of plant development and response to external stimuli. Extensive phosphorylation of LRR-RK cytoplasmic domains is among the earliest detectable responses following ligand perception, and reciprocal transphosphorylation between a receptor and its co-receptor is thought to activate the receptor complex. Originally proposed based on characterization of the brassinosteroid receptor, the prevalence of complex activation via reciprocal transphosphorylation across the plant RK family has not been tested. Using the LRR-RK ELONGATION FACTOR TU RECEPTOR (EFR) as a model RK, we set out to understand the steps critical for activating RK complexes. While the EFR cytoplasmic domain is an active protein kinase in vitro and is phosphorylated in a ligand-dependent manner in vivo, catalytically deficient EFR variants are functional in anti-bacterial immunity. These results reveal a non-catalytic role for the EFR cytoplasmic domain in triggering immune signaling and indicate that reciprocal transphoshorylation is not a ubiquitous requirement for LRR-RK complex activation. Rather, our analysis of EFR along with a detailed survey of the literature suggests a distinction between LRR-RK complexes with RD- versus non-RD protein kinase domains. Based on newly identified phosphorylation sites that regulate the activation state of the EFR complex in vivo, we propose that LRR-RK complexes containing a non-RD protein kinase may be regulated by phosphorylation-dependent conformational changes of the ligand-binding receptor which could initiate signaling in a feed-forward fashion either allosterically or through driving the dissociation of negative regulators of the complex.

biochemistry↗

bioRxiv2020

The transcriptional landscape of Arabidopsis thaliana pattern-triggered immunity

Plants initiate immunity upon recognition of a wide array of self and non-self molecular patterns. Whether plants tune their immune outputs to patterns of different biological origins or of different biochemical nature remains mostly unclear. Here, we performed a detailed early time-series transcriptomics analysis in Arabidopsis thaliana, revealing that the response to diverse patterns is remarkably congruent. Early transcriptional reprogramming is dominated by a plant general stress response (GSR), which is essential for pattern-induced immunity. The definition of core immunity response genes common and specific to pattern response in addition revealed the function of previously uncharacterized GLUTAMATE RECEPTOR-LIKE calcium-permeable channels in immunity. This study thus illustrates general and unique properties of early immune transcriptional reprogramming and uncovered important components of plant immunity. One Sentence SummaryTime-resolved transcriptomics reveals new properties of pattern-triggered immunity and function of calcium-permeable channels.

plant biology↗