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S. coelicolor Wild Type R5- Medium Time-course Study

ABSTRACT: Many biological processes are intrinsically dynamic, incurring profound changes at both molecular and physiological levels. Systems analyses of such processes incorporating large-scale transcriptome or proteome profiling can be quite revealing. Although consistency between mRNA and proteins is often implicitly assumed in such studies, instances of divergent trends are frequently observed indicating the existence of post-transcriptional regulation. Here, we present a comparative transcriptome and proteome analysis of growth and stationary phase adaptation in Streptomyces coelicolor, taking the time-dynamics of process into consideration. These processes are of immense interest in streptomycetes as they encompass the physiological transformations eliciting biosynthesis of many naturally occurring therapeutic agents. A shotgun proteomics approach based on mass spectrometric analysis of isobaric stable isotope labeled peptides iTRAQ(TM) enabled identification and rapid quantification of approximately 14% of the theoretical proteome of S. coelicolor. Independent principal component analyses of this and DNA microarray-derived transcriptome data revealed that the prominent patterns in both protein and mRNA domains are surprisingly well correlated. Despite this general consensus, by employing a systematic concordance analysis we estimated that over 30% of the analyzed genes likely exhibited significantly divergent patterns, of which nearly one-third displayed even opposing trends. Integrating this data with biological information, we discovered that certain groups of functionally related genes were co-regulated independently as mRNA and/or proteins despite observations of apparent mRNA-protein discordance. This clearly suggests that post-transcriptional regulatory mechanisms are prominent even amongst prokaryotes while reaffirming the plausibility of such mechanisms acting in a concerted fashion at a protein complex or sub-pathway level. Keywords: Time course

ORGANISM(S): Streptomyces coelicolor

PROVIDER: GSE7172 | GEO | 2007/06/08

SECONDARY ACCESSION(S): PRJNA98253

REPOSITORIES: GEO

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Project description:Many biological processes are intrinsically dynamic, incurring profound changes at both molecular and physiological levels. Systems analyses of such processes incorporating large-scale transcriptome or proteome profiling can be quite revealing. Although consistency between mRNA and proteins is often implicitly assumed in such studies, instances of divergent trends are frequently observed indicating the existence of post-transcriptional regulation. Here, we present a comparative transcriptome and proteome analysis of growth and stationary phase adaptation in Streptomyces coelicolor, taking the time-dynamics of process into consideration. These processes are of immense interest in streptomycetes as they encompass the physiological transformations eliciting biosynthesis of many naturally occurring therapeutic agents. A shotgun proteomics approach based on mass spectrometric analysis of isobaric stable isotope labeled peptides iTRAQ(TM) enabled identification and rapid quantification of approximately 14% of the theoretical proteome of S. coelicolor. Independent principal component analyses of this and DNA microarray-derived transcriptome data revealed that the prominent patterns in both protein and mRNA domains are surprisingly well correlated. Despite this general consensus, by employing a systematic concordance analysis we estimated that over 30% of the analyzed genes likely exhibited significantly divergent patterns, of which nearly one-third displayed even opposing trends. Integrating this data with biological information, we discovered that certain groups of functionally related genes were co-regulated independently as mRNA and/or proteins despite observations of apparent mRNA-protein discordance. This clearly suggests that post-transcriptional regulatory mechanisms are prominent even amongst prokaryotes while reaffirming the plausibility of such mechanisms acting in a concerted fashion at a protein complex or sub-pathway level. Keywords: Time course Time-course study involved analysis of 8 samples (7h, 11h, 14h, 16h, 22h, 26h, 34h, 38h). Of these, 14h, 22h, 26h and 38h were analyzed in duplicate arrays. All arrays used cDNA labeled with Alexa647 and gDNA labeled with Cy3.

Project description:Background The genomes of Streptomyces coelicolor and Streptomyces lividans bear a considerable degree of orthology. While S. coelicolor is the model streptomycete for studying antibiotic synthesis and differentiation, S. lividans is almost exclusively considered as the preferred host, among actinomycetes, for cloning and expression of exogenous DNA. We used whole genome microarrays as a comparative genomics tool for identifying the subtle yet crucial differences between these two chromosomes. Results We identified five large S. coelicolor genomic islands (≥25 kb) and 18 smaller islets absent in S. lividans chromosome. Many of these regions show anomalous GC bias and codon usage patterns. Six of them are in close vicinity of tRNA genes while nine are flanked with near perfect repeat sequences indicating that these are probable recent evolutionary acquisitions into S. coelicolor. Embedded within these segments are at least four DNA methylases and two probable methyl-sensing restriction endonucleases. Comparison with S. coelicolor transcriptome and proteome data revealed that some of the missing genes are active during the course of growth and differentiation in S. coelicolor. In particular, a pair of methylmalonyl CoA mutase (mcm) genes involved in polyketide precursor biosynthesis, an acyl-CoA dehydrogenase implicated in timing of actinorhodin synthesis and bldB, a developmentally significant regulator whose mutation causes complete abrogation of antibiotic synthesis belong to this category. Conclusion Our findings provide tangible hints for elucidating the genetic basis of important phenotypic differences between these two streptomycetes. Importantly, absence of certain genes in S. lividans identified here could potentially explain the relative ease of DNA transformations or the conditional lack of actinorhodin synthesis in S. lividans. Further genetic studies based on these results will enable one to target specific sequences in the genetically well-characterized S. coelicolor to adapt it for industrial processes. Keywords: Comparative Genomic Hybridization

Project description:Chronic obstructive pulmonary disease (COPD) is one of the most prevalent lung diseases, and involves persistent airflow limitation and incorporates both emphysema and chronic bronchitis. Cigarette smoking has been identified as the main risk factor for disease development and progression. In a basic model of COPD, the disease is initiated when the physiologic response mechanisms to cigarette smoke exposure are overwhelmed; for example, because of long-term exposure effects or other aging-related changes. In this parallel-group case-controlled clinical study we asked to what extent the different transitions in a chronic-exposure-to-disease model are reflected in the proteome and cellular transcriptome of induced sputum samples from the lung. For this, we selected 60 age- and gender-matched individuals for each of four study groups: current healthy smokers, current-smoker COPD patients, former smokers, and never smokers (a total of 240 individuals). Induced sputum was collected, the cell-free supernatant was analyzed by quantitative proteomics (isobaric-tag based), and the cellular mRNA fraction was analyzed by microarray-based expression profiling. The sputum proteome of current smokers (healthy or COPD patients) clearly reflected the common physiological responses to smoke exposure, including alterations in mucin/trefoil proteins (e.g., MUC5AC and TFF1/3up-regulation), peptidase regulators (e.g., TIMP1 up-regulation), and a prominent xenobiotic/oxidative stress response (e.g., NQO1 and ALDH3A1 up-regulation). The latter response also was observed in the sputum transcriptome, which additionally demonstrated an immune-related polarization change (toward a M2 signature). The (long-term) former smoker group showed nearly complete reversal of the observable biological effects. Thirteen differentially abundant proteins between the COPD and healthy smoker groups were identified. These abundant proteins included previously reported COPD-associated proteins (e.g., TIMP1 (up-regulation) and APOA1 (down-regulation)) and novel proteins such as C6orf58 and BPIFB1 (LPLUNC1) (both up-regulated in the COPD group compared with the healthy smokers). In summary, our study demonstrates that sputum proteomics/transcriptomics can capture the complex and reversible physiological response to cigarette smoke exposure, which appears to be only slightly modulated in early-stage COPD patients. The study has been registered on ClinicalTrials.gov with identifier NCT01780298.

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S. coelicolor Wild Type R5- Medium Time-course Study

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