Project description:We identified Sox17 as a novel angiogenic transcription factor in the context of tumor. Our data revealed that Sox17 promotes tumor angiogenesis and tumor vessel abnormality. We found that Sox17 is specifically expressed in tumor endothelial cells within tumors. Our study elucidates a novel transcriptional regulation for tumor angiogenesis Control HUVECs vs. Sox17 knockdown HUVECs. Biological replicates: 3 control replicates, 3 transfected replicates.
Project description:These data suggest that co-culture with macrophages increases expression of NDRG-1 in epithelial cell lines. The finding is confirmed in 1 mouse epithelial cell line, and in tissue derived from mice genetically and dietetically altered to increase macrophage infiltration of the small and large intestinal epithelium. NDRG1 is identified as a potential mediator of macrophage effects on tumorigenesis in the large and small intestine. Array data is part of a larger study involving the effects of Vitamin D, in concert with macrophages, on intestinal homeostasis and tumorigenesis, entitled Cell autonomous and non-autonomous interactions of a western-style diet and the vitamin D receptor in intestinal homeostasis and tumorigenesis Cells from human colon cancer cell lines were cultured either alone, with Vitamin D3, with THP1 macrophages, or with THP1 macrophages and Vitamin D3, in a system which allowed no physical contact but exchange of soluble factors between the cell types.
Project description:To elucidate that ShosTA exerts an anti-phage function, we further explored the interacting proteins of ShosA. IP-MS/MS analysis reveals in vivo interactions between ShosA and some recombination-associated proteins. FLAG-tagged ShosA in the context of the full ShosTA system or FLAG-tag alone are used.
Project description:Many eukaryotic viruses require membrane-bound compartments for replication, but no such organelles are known to be formed by prokaryotic viruses1–3. Bacteriophages of the Chimalliviridae family sequester their genomes within a phage-generated organelle, the phage nucleus, which is enclosed by a lattice of the viral protein ChmA4–10. Previously, we observed lipid membrane-bound vesicles in cells infected by Chimalliviridae, but due to the paucity of genetics tools for these viruses it was unknown if these vesicles represented unproductive, abortive infections or a bona fide stage in the phage life cycle. Using the recently-developed dRfxCas13d-based knockdown system CRISPRi-ART11 in combination with fluorescence microscopy and cryo-electron tomography, we show that inhibiting phage nucleus formation arrests infections at an early stage in which the injected phage genome is enclosed within a membrane-bound early phage infection (EPI) vesicle. We demonstrate that early phage genes are transcribed by the virion-associated RNA polymerase from the genome within the compartment, making the EPI vesicle the first known example of a lipid membrane-bound organelle that separates transcription from translation in prokaryotes. Further, we show that the phage nucleus is essential for the phage life cycle, with genome replication only beginning after the injected DNA is transferred from the EPI vesicle to the newly assembled phage nucleus. Our results show that Chimalliviridae require two sophisticated subcellular compartments of distinct compositions and functions that facilitate successive stages of the viral life cycle.
Project description:Bacteriophages are increasingly recognised as key players in modulating plant-microbe interactions, including their potential in the biocontrol of plant pathogenic bacteria. In this study, we investigated the tripartite interaction between, Arabidopsis thaliana, the bacterial plant pathogen Xanthomonas campestris pv. campestris (Xcc), and the lytic phage Seregon. Using meta-transcriptomic profiling, we characterized host and pathogen responses during infection and phage treatment. While a single phage treatment did not lead to the eradication of Xcc, treatment with phage Seregon significantly mitigated Xcc-induced disease symptoms, restoring leaf growth to levels comparable to the uninfected control within 14 days post-inoculation. Our data revealed that phage-mediated protection is associated with early bacterial recognition and suppression of jasmonate (JA)-related responses in the host. Analysis of nuclear localized reporter plant cell lines further confirmed a significant reduction in ROS levels in phage-treated plants. Concurrently, Xcc exhibited significant transcriptional downregulation of key virulence factors in the presence of the phage, including the genes encoding the type III secretion system, its associated effectors, and components involved in flagella biosynthesis. Remarkably, phage treatment did not lead to a significant increase in bacterial resistance to phage infection, which is in stark contrast to in vitro conditions. Taken together, this study provides first mechanistic insight into how phages can be harnessed to shape plant-pathogen interactions and highlights their potential role in enhancing plant resilience through targeted modulation of both host immunity and pathogen behaviour.
Project description:Bacteriophages (phages) significantly influence bacterial populations in their natural environment. However, one aspect that has not been thoroughly explored in the context of phage-bacteria interactions is the post-transcriptional regulation of gene expression, despite the growing attention it has received for bacterial physiology over the last two decades. Important players in this process are small RNAs (sRNAs) that regulate target mRNAs via base-pairing, typically using RNA chaperones like Hfq to facilitate this regulation. Here, we apply RIL-seq, to map in-vivo the sRNA-RNA network in Escherichia coli upon lambda phage infection. We highlight changes in the bacterial transcriptome and sRNA interactome while uncovering a novel phage-encoded sRNA that regulates key genes in E. coli. We decipher the molecular mechanism of the sRNA-mediated regulation and illustrate how it hijacks the host replication machinery and helps the infection cycle. Overall, we uncover an RNA-level regulatory layer that shapes the E. coli - lambda interactions.
Project description:Bacteriophages (phages) significantly influence bacterial populations in their natural environment. However, one aspect that has not been thoroughly explored in the context of phage-bacteria interactions is the post-transcriptional regulation of gene expression, despite the growing attention it has received for bacterial physiology over the last two decades. Important players in this process are small RNAs (sRNAs) that regulate target mRNAs via base-pairing, typically using RNA chaperones like Hfq to facilitate this regulation. Here, we apply RIL-seq, to map in-vivo the sRNA-RNA network in Escherichia coli upon lambda phage infection. We highlight changes in the bacterial transcriptome and sRNA interactome while uncovering a novel phage-encoded sRNA that regulates key genes in E. coli. We decipher the molecular mechanism of the sRNA-mediated regulation and illustrate how it hijacks the host replication machinery and helps the infection cycle. Overall, we uncover an RNA-level regulatory layer that shapes the E. coli - lambda interactions.
Project description:We identified Sox17 as a novel angiogenic transcription factor in the context of tumor. Our data revealed that Sox17 promotes tumor angiogenesis and tumor vessel abnormality. We found that Sox17 is specifically expressed in tumor endothelial cells within tumors. Our study elucidates a novel transcriptional regulation for tumor angiogenesis