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: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: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:Directed evolution in mammalian cells can facilitate the engineering of mammalian-compatible biomolecules and can enable synthetic evolvability for mammalian cells. We engineered an orthogonal alphaviral RNA replication system to evolve synthetic RNA-based devices, enabling RNA replicase-assisted continuous evolution (REPLACE) in live mammalian cells. Toinvestigatetheexpressionheterogeneityofself-replicatingRNAsinrepRNA-v4cells,weperformedsingle-cellRNA-seqanalysisusingthe10xGenomicssequencingmethod.Ouranalysisofthesingle-cellRNA-seqprofilingdatarevealedarelativelyuniformexpressionpatternofself-replicatingRNAswithinrepRNA-v4cells.
2024-07-07 | GSE235341 | GEO
Project description:Lysosome-targeting chimeras (LYTACs) are a promising therapeutic modality to drive the degradation of extracellular proteins. However, early versions of LYTAC contain synthetic glycopeptides that cannot be genetically encoded. Here we present our designs for a fully genetically encodable LYTAC (GELYTAC), making our tool compatible with integration into therapeutic cells for targeted delivery at diseased sites. To achieve this, we replaced the glycopeptide portion of LYTACs with the protein insulin like growth factor 2 (IGF2). After showing initial efficacy with wild type IGF2, we increased the potency of GELYTAC using directed evolution. Subsequently, we demonstrated that our engineered GELYTAC construct not only secretes from HEK293T cells but also from human primary T-cells to drive the uptake of various targets into receiver cells. Immune cells engineered to secrete GELYTAC thus represent a promising avenue for spatially-selective targeted protein degradation.
2024-02-27 | MSV000094184 | MassIVE
Project description:Cance vaccines have become a milestone in immunotherapy, but inadequate activation rate of antigen presenting cells (APCs) and low delivery efficiency of specific antigen have widely limited their clinical application. Here we design an engineered vaccine platform based on targeted delivery of specific antigens to activated APCs. This vaccine platform is implemented by loading stimulator of interferon genes agonist and tumor lysate protein with calcium phosphate as adjuvants, and coating the surface with mannose-modified liposomes. By loading different types of tumor antigen proteins, this nanovaccine platform successfully achieves tumor immunotherapy in breast and colon cancer bearing mice. In addition, personalized nanovaccine prepared from surgically removed tumor lysate proteins also significantly suppresses postsurgical distant tumor. Through the design of nanovaccine platform, we provide an efficient multi-adjuvant delivery platform for multiple types of tumor antigens, and also offer more ideas for personalized vaccine immunization. This nanovaccine platform has great prospects for transformation due to the designability and simplicity for the preparation.
2024-05-14 | GSE267162 | GEO
Project description:Targeted immunosuppression enhances repeated gene delivery
| PRJNA823700 | ENA
Project description:Genome editing tools with high precision are key to develop improved crops but current technologies to place new DNA into specific locations in plant genomes are low frequency and error-prone. Transposable elements (TEs) evolved to insert their DNA seamlessly into genomes, albeit in a quasi-random pattern. We developed a genome engineering tool that controls the TE insertion site and subsequently the delivery of any cargo attached to this TE. Using our tool, we demonstrated sequence-specific targeted delivery (guided by the CRISPR gRNA) of enhancers, an open reading frame and gene expression cassette into the genome of the model plant Arabidopsis, and we translated this technology to the crop soybean. We have engineered a ‘junk’ TE into a useful and accessible toolkit that enables the sequence-specific targeting of custom DNA into plant genomes.
2024-05-03 | GSE227103 | GEO
Project description:Genome editing tools with high precision are key to develop improved crops but current technologies to place new DNA into specific locations in plant genomes are low frequency and error-prone. Transposable elements (TEs) evolved to insert their DNA seamlessly into genomes, albeit in a quasi-random pattern. We developed a genome engineering tool that controls the TE insertion site and subsequently the delivery of any cargo attached to this TE. Using our tool, we demonstrated sequence-specific targeted delivery (guided by the CRISPR gRNA) of enhancers, an open reading frame and gene expression cassette into the genome of the model plant Arabidopsis, and we translated this technology to the crop soybean. We have engineered a ‘junk’ TE into a useful and accessible toolkit that enables the sequence-specific targeting of custom DNA into plant genomes.
2024-05-03 | GSE227104 | GEO