Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1287998 | ENA |
REPOSITORIES: ENA
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Project description:Due to low numbers and poor accessibility of host cells that are targeted for effector delivery, the actual biological functions of most effectors remain elusive. Here, we developed a novel Isolation Nuclei TArgeted by Bacterial Effectors (INTABE) system, which facilitates selectively recovering nuclei of the cells in Arabidopsis thaliana plants that have received type-III effectors of pathogenic Xanthomonas bacteria. Using these nuclei as studying materials, we analysed changes in host gene expression and their correlation with changes in DNA methylation induced by Xanthomonas effector Outer Protein D (XopD).
2022-10-22 | E-MTAB-10281 | biostudies-arrayexpress
Project description:Immunotherapy based on live microorganisms has shown promise in preclinical studies, but its clinical translation has been hampered by limited efficacy and innegligible toxicity. Here, we developed M-BLAST (Macrophage-Bacteria encapsulation Lytic Autoactivated Synergistic Therapeutics), a dual-gated macrophage-mediated bacterial tumor-targeted delivery and in situ activation system. M-BLAST incorporates density-regulated virulence-enhanced attenuated Salmonella strains as the therapeutic core, thermally-controlled GSDMD-N-expressing macrophages as the delivery vector, and copper selenide, a photothermal material, as a heat-shock “primer.” Following systemic administration, localized near-infrared irradiation at the tumor site triggers macrophage pyroptosis, ensuring rapid and complete bacterial release. This disrupts the immunosuppressive tumor microenvironment and elicits a widespread cascading antitumor response just like a “immune bomb”, while dual-gating design of bacterial density and heat-shock ensures safety by preventing off-target activation in non-tumor regions. M-BLAST promises to enhance the therapeutic utility of living engineered bacteria for cancer while ensuring safety.
2025-12-19 | GSE291419 | GEO
Project description:The probiotic strain Escherichia coli Nissle 1917 (EcN), a potential member of tumor-targeting bacteria, shows great promise for cancer treatment. By leveraging engineered EcN, we can design a bacteria-assisted, tumor-targeted therapy for the biosynthesis and targeted delivery of small-molecule anticancer agents. In this study, we aimed to use EcN as a base for synthesizing Romidepsin (FK228), an FDA-approved drug originally made by Chromobacterium violaceum No. 96. Through gene cluster reconstruction, promoter optimization, and genome modification, we created FK228-producing strains to boost anticancer efficacy. The engineered strain achieved a maximum in vitro yield of 1.5 mg/L. In 4T1 tumor-bearing BALB/c mouse xenograft models , six recombinant strains outperformed the wild-type EcN. Proteome showed that inflammatory response induced by EcN combined with intratumoral FK228 production improved treatment results. Also, targeted synthesis reduced FK228's cardiotoxicity and mortality. Engineered EcN enables drug biosynthesis and precise delivery, offering powerful anticancer activity.
2026-02-14 | PXD073783 | Pride
Project description:ntroduction: Recent studies have discovered lung cancer subtypes to have their own profile of microbiome within the tumor microenvironment. Additionally, the tumor associated microbiome exhibited altered bacterial pathways, suggesting that certain bacterial families are more fit to facilitate tumor progression than others. We believe that there exists a crosstalk between lung adenocarcinoma cells (LUAD) and bacterial cells. Methods and Materials: RNA-seq was performed on LUAD cell lines to understand the paracrine signaling effects that bacterial biomolecules have. From our RNA-seq data, we chose to investigate glycolysis by measuring glucose uptake and lactate production, investigate invasive potential through invasion assays, and measure EMT markers. As lipopolysaccharides (LPS) are found abundantly on the cell wall of gram-negative bacteria and can activate toll like receptor 4 (TLR4), we inhibited TLR4 with C34 to determine the relationship between TLR4 and the phenotypic changes. Finally, to gain a better understanding of the bacterial biomolecules leading to the changes observed, we treated our media with either RNAse, charcoal, or dialyzed molecules > 3kDa. Results and Discussion: From our RNA-seq data, we observed a total of 948 genes upregulated in the presence of E. coli biomolecules. Of the 948 upregulated genes observed in LUAD cell lines incubated in E. coli biomolecules, we witnessed increased expression of Hexokinase II, JUN proto-oncogene, and Snail Family Transcriptional Repressor 1. We verified the elevation of glycolytic enzymes through western blot and saw elevation of 2-deoxyglucose uptake and lactate production in LUAD cell lines incubated in E. coli biomolecules using scintillation counter and lactate luminescence assay, respectively. In addition to E. coli elevating glycolysis in LUAD cell lines, we also saw increase in invasive potential by Boyden chamber. Inhibition of TLR4 did not lead to decreasing the impact of E. coli biomolecules on glycolysis or invasive potential of LUAD. Modulating our E. coli supplemented media with either RNAse, dextran-coated charcoal, or using a spin column to remove biomolecules < 3kDa resulted in changes in HKII and Claudin protein expression. Overall, these findings indicate a direct relationship between E. coli and LUAD, wherein several well-known hallmarks of cancer are upregulated. Future studies would do well in investigating these molecules further and fully understanding the impact of a microbial shift in the tumor microenvironment.
2025-02-19 | GSE286573 | GEO
Project description:Due to low numbers and poor accessibility of host cells that are targeted for effector delivery, the actual biological functions of most effectors remain elusive. Here, we developed a novel Isolation Nuclei TArgeted by Bacterial Effectors (INTABE) system, which facilitates selectively recovering nuclei of the cells in Arabidopsis thaliana plants that have received type-III effectors of pathogenic Xanthomonas bacteria. Using these nuclei as studying materials, we analysed changes in host gene expression and their correlation with changes in DNA methylation induced by Xanthomonas effector Outer Protein D (XopD).
2022-10-22 | E-MTAB-10280 | biostudies-arrayexpress
Project description:Understanding the spatial organization of biomolecules in living organisms is a central but challenging goal in biology. Here we introduce Peroxidase Reactions Activated by D-amino Acids (PRADA), which uses an engineered oxidase to convert non-proteinogenic D-amino acid into H2O2 for in situ activation of a genetically fused peroxidase. PRADA enables versatile proximity-based chemistries, including protein labeling, RNA labeling, and functional polymer assembly, with minimal toxicity and background. We demonstrate that PRADA is broadly applicable inside living organisms, including flies, worms, fish, and mice. By further leveraging a unique RNA reactivity of PRADA, we develop a mutational profiling sequencing strategy for spatiotemporally-resolved mapping of RNA secondary structure. Application of this multifaceted PRADA platform in a mouse tumor model offered insights into its mitochondrial proteome, transcriptome, and RNA structurome, revealing distinct RNA folding pattern as a critical layer of mitochondrial gene expression regulation. Collectively, the application of PRADA in diverse systems holds promise to uncover the intricate organization of biomolecules in vivo.
2026-07-31 | GSE295471 | GEO
Project description:Understanding the spatial organization of biomolecules in living organisms is a central but challenging goal in biology. Here we introduce Peroxidase Reactions Activated by D-amino Acids (PRADA), which uses an engineered oxidase to convert non-proteinogenic D-amino acid into H2O2 for in situ activation of a genetically fused peroxidase. PRADA enables versatile proximity-based chemistries, including protein labeling, RNA labeling, and functional polymer assembly, with minimal toxicity and background. We demonstrate that PRADA is broadly applicable inside living organisms, including flies, worms, fish, and mice. By further leveraging a unique RNA reactivity of PRADA, we develop a mutational profiling sequencing strategy for spatiotemporally-resolved mapping of RNA secondary structure. Application of this multifaceted PRADA platform in a mouse tumor model offered insights into its mitochondrial proteome, transcriptome, and RNA structurome, revealing distinct RNA folding pattern as a critical layer of mitochondrial gene expression regulation. Collectively, the application of PRADA in diverse systems holds promise to uncover the intricate organization of biomolecules in vivo.
2026-07-31 | GSE319782 | GEO
Project description:Understanding the spatial organization of biomolecules in living organisms is a central but challenging goal in biology. Here we introduce Peroxidase Reactions Activated by D-amino Acids (PRADA), which uses an engineered oxidase to convert non-proteinogenic D-amino acid into H2O2 for in situ activation of a genetically fused peroxidase. PRADA enables versatile proximity-based chemistries, including protein labeling, RNA labeling, and functional polymer assembly, with minimal toxicity and background. We demonstrate that PRADA is broadly applicable inside living organisms, including flies, worms, fish, and mice. By further leveraging a unique RNA reactivity of PRADA, we develop a mutational profiling sequencing strategy for spatiotemporally-resolved mapping of RNA secondary structure. Application of this multifaceted PRADA platform in a mouse tumor model offered insights into its mitochondrial proteome, transcriptome, and RNA structurome, revealing distinct RNA folding pattern as a critical layer of mitochondrial gene expression regulation. Collectively, the application of PRADA in diverse systems holds promise to uncover the intricate organization of biomolecules in vivo.
2026-07-31 | GSE319436 | GEO
Project description:Adeno-associated viruses (AAVs) are foundational gene delivery tools for basic science and clinical therapeutics. However, lack of mechanistic insight, especially for engineered vectors created by directed evolution, can hamper their application. Here, we adapted an unbiased human cell microarray platform to determine the extracellular and cell surface interactomes of natural and engineered AAVs. We identified a naturally-evolved and serotype-specific interaction of AAV9 with human interleukin 3 (IL3), with possible roles in host immune modulation, as well as lab-evolved low-density-lipoprotein-receptor-related-protein 6 (LRP6) interactions specific to engineered capsids that cross the blood-brain barrier in non-human primates upon intravenous administration. The unbiased cell microarray screening approach also allowed us to identify off-target tissue binding interactions of engineered brain-enriched AAVs that may inform vectors’ peripheral organ tropism and side effects. These results allow confident application of engineered AAVs in diverse organisms and unlock future target-informed engineering of improved viral and non-viral vectors for non-invasive therapeutic delivery to the brain.
2024-07-31 | PXD045380 | Pride
Project description:The circumvention of tissue-specific toxicity while improving selectivity remains a significant challenge in cancer therapy. Antibody-assisted delivery of chemotypes aims to address this, leading to several approved therapies; however, non-specific payload release and poor solid tumour penetration necessitate alternative approaches. To this end, we engineered a ligand-targeted drug conjugate, exploiting the over-expression of the prostate-specific membrane antigen (PSMA) in prostate cancer to selectively deliver and conditionally release RT53, a highly specific epigenetic inhibitor of the bromo and extra-terminal (BET) proteins. RT53 phenocopies the effects of the well characterized IBET pan-BET inhibitor in vitro and in vivo, arresting cellular growth and downregulating solute carriers, while exhibiting antitumor activity in subcutaneous ectopic prostate cancer mouse models. Importantly, PSMA-targeted delivery and conditional release of RT53 achieves superior efficacy in vivo ameliorating on-target, off-tissue toxicity, and establishing proof-of-concept for the targeted delivery of small molecule epigenetic chemotherapeutics.
2026-08-27 | GSE279011 | GEO