Project description:In order to more accurately discover the cause of drug resistance in tumor treatment, and to provide a new basis for precise treatment.
Therefore, based on the umbrella theory of precision medicine, we carried out this single-center, prospective, and observational study to include patients with liver metastases from colorectal cancer. By combining genome, transcriptome, and proteomic sequencing data, we established a basis for colorectal cancer liver Transfer the multi-omics data of the sample, describe the reason for the resistance of the first-line treatment, and search for new therapeutic targets.
Project description:We performed ribosome profiling which is the deep-sequencing of mRNA fragments protected by translating ribosome for two Streptomyces species through different growth phases to provide the translatome data
Project description:Specialized biosynthetic gene clusters in Streptomyces are subject to complex regulation involving both transcriptional control and chromosome organization. The nucleoid-associated protein Lsr2 silences many of these clusters, yet how it shapes the global chromatin structure and how its conserved paralog LsrL contributes to this process remain poorly understood. In this study, we applied a multi-omics approach, combining transcriptional activity, genome-wide protein-DNA binding profiles, and three-dimensional chromosome conformation to characterize the coordination of Lsr2 and LsrL in exerting transcriptional control and genome architecture in Streptomyces venezuelae. In line with established Lsr2 functions, we find that Lsr2 sets broad transcriptional boundaries, while LsrL acts in a more context-specific manner that depends on the presence of Lsr2 and may function to reinforce or modulate Lsr2-mediated silencing. Loss of Lsr2 reshaped the chromatin landscape genome-wide, relieving its restriction on short-range contacts, triggering strong transcriptional changes and new domain boundaries near de-repressed BGCs. These findings establish Lsr2 as a dominant but contextually modulated regulator whose interplay with LsrL coordinates specialized metabolism with higher-order chromosome organization.
Project description:Specialized biosynthetic gene clusters in Streptomyces are subject to complex regulation involving both transcriptional control and chromosome organization. The nucleoid-associated protein Lsr2 silences many of these clusters, yet how it shapes the global chromatin structure and how its conserved paralog LsrL contributes to this process remain poorly understood. In this study, we applied a multi-omics approach, combining transcriptional activity, genome-wide protein-DNA binding profiles, and three-dimensional chromosome conformation to characterize the coordination of Lsr2 and LsrL in exerting transcriptional control and genome architecture in Streptomyces venezuelae. In line with established Lsr2 functions, we find that Lsr2 sets broad transcriptional boundaries, while LsrL acts in a more context-specific manner that depends on the presence of Lsr2 and may function to reinforce or modulate Lsr2-mediated silencing. Loss of Lsr2 reshaped the chromatin landscape genome-wide, relieving its restriction on short-range contacts, triggering strong transcriptional changes and new domain boundaries near de-repressed BGCs. These findings establish Lsr2 as a dominant but contextually modulated regulator whose interplay with LsrL coordinates specialized metabolism with higher-order chromosome organization.
Project description:Specialized biosynthetic gene clusters in Streptomyces are subject to complex regulation involving both transcriptional control and chromosome organization. The nucleoid-associated protein Lsr2 silences many of these clusters, yet how it shapes the global chromatin structure and how its conserved paralog LsrL contributes to this process remain poorly understood. In this study, we applied a multi-omics approach, combining transcriptional activity, genome-wide protein-DNA binding profiles, and three-dimensional chromosome conformation to characterize the coordination of Lsr2 and LsrL in exerting transcriptional control and genome architecture in Streptomyces venezuelae. In line with established Lsr2 functions, we find that Lsr2 sets broad transcriptional boundaries, while LsrL acts in a more context-specific manner that depends on the presence of Lsr2 and may function to reinforce or modulate Lsr2-mediated silencing. Loss of Lsr2 reshaped the chromatin landscape genome-wide, relieving its restriction on short-range contacts, triggering strong transcriptional changes and new domain boundaries near de-repressed BGCs. These findings establish Lsr2 as a dominant but contextually modulated regulator whose interplay with LsrL coordinates specialized metabolism with higher-order chromosome organization.
Project description:The genomic and proteomic analyses of Streptomyces lividans strains deficient in the major signal peptidase SipY or in the translocase complex protein SecG resulted in a set of genes being equally regulated. These genes are apparently responsible for the common deficiencies in extracellular protein production and sporulation shared by both mutant strains, constituting a cellular response to the stress caused by the potential malfunction of the translocase complex, which we have named “extracellular protein translocation stress (EPTS)”.
Project description:Background Streptomyces are key contributors to soil microbiome function, known for their biosynthetic diversity. While advances in -omics technologies have improved our understanding of microbiome composition and metabolic potential, the mechanisms underpinning interspecies interactions remain poorly resolved. Here, we investigate the molecular basis of interactions among four sympatric Streptomyces soil microbiome isolates, focusing on phenotypic, metabolomic and transcriptomic responses. Results Co-culture experiments revealed that one isolate, strain A, exhibited pronounced phenotypic changes when grown alongside each of the other three strains. Untargeted metabolomics and RNA-seq analyses showed that strain A undergoes distinct metabolic and transcriptional shifts depending on its partner, with the strongest response elicited by strain C. Despite all four strains possessing a conserved desferrioxamine biosynthetic gene cluster, only strain C constitutively produced desferrioxamine B (DFO-B), a hydroxymate siderophore, indicating a role of iron bioavailability in the interaction. Supplementation with DFO-B or iron mimicked the growth stimulation of strain A observed in co-culture with strain C, and CRISPR base editing of desD in strain C abolished both DFO production and the phenotypic induction of strain A. However, transcriptomic profiles of strain A varied significantly depending on the partner strain, with distinct sets of biosynthetic gene clusters and metabolic pathways activated in response to strains B and C, suggesting additional cues beyond DFO-B. In contrast, strain D did not elicit growth stimulation in its partners, and itself showed downregulation of amino acid and carbon metabolism when co-cultured with strain C. These findings indicate that Streptomyces interactions are not only mediated by siderophore piracy but also involve complex, strain-specific molecular responses. Conclusions Our findings demonstrate that Streptomyces interactions are highly strain-specific and only partly mediated by siderophore piracy, with DFO-B acting as a potent interspecies cue. The divergent molecular responses to different partners suggest nuanced mechanisms of microbial sensing and competition. These insights advance our understanding of microbial crosstalk and highlight the ecological and evolutionary complexity of siderophore-mediated interactions. By integrating transcriptomics, metabolomics, and biochemical assays, we present a robust framework for dissecting microbial interactions, with implications for microbiome engineering and synthetic community design.
Project description:Two component sensor-response regulator systems (TCSs) are very common in the genomes of the Streptomyces species that have been fully sequenced to date. It has been suggested that this large number is an evolutionary response to the variable environment that Streptomyces encounter in soil. Notwithstanding this, TCSs are also more common in the sequenced genomes of other Actinomycetales when these are compared to the genomes of most other eubacteria. In this study, we have used DNA/DNA genome microarray analysis to compare fourteen Streptomyces species and one closely related genus to Streptomyces coelicolor in order to identify a core group of such systems. This core group is compared to the syntenous and non-syntenous TCSs present in the genome sequences of other Actinomycetales in order to separate the systems into those present in Actinomycetales in general, the Streptomyces specific systems and the species specific systems. Horizontal transfer does not seem to play a very important role in the evolution of the TCS complement analyzed in this study. However, cognate pairs do not necessarily seem to evolve at the same pace, which may indicate the evolutionary responses to environmental variation may be reflected differently in sequence changes within the two components of the TCSs. The overall analysis allowed subclassification of the orphan TCSs and the TCS cognate pairs and identification of possible targets for further study using gene knockouts, gene overexpression, reporter genes and yeast two hybrid analysis.