Project description:We report the application of a high-throughput technique, RNA-seq, to study the transcriptomic response of P. putida DOT-T1E and E. coli growing in co-cultures
Project description:All cells must detect, interpret and adapt to multiple and concurrent stimuli. While signaling pathways are highly specialized, different pathways often share components or have components with overlapping functions. In the yeast Saccharomyces cerevisiae, the high osmolarity glycerol (HOG) pathway has two seemingly redundant branches, mediated by Sln1 and Sho1. Both branches are activated by osmotic pressure, leading to phosphorylation of the MAPKs Hog1 and Kss1. The mating pathway is activated by pheromone, leading to phosphorylation of the MAPKs Fus3 and Kss1. Given that Kss1 is shared by the two pathways, we investigated its role in signal coordination. We activated both pathways with a combination of salt and pheromone, in cells lacking the shared MAPK and in cells lacking either of the redundant branches of the HOG pathway. By systematically evaluating MAPK activation, translocation, and transcription programs, we determined that Sho1 mediates cross talk between the HOG and mating pathways and does so through Kss1. Further, we show that Kss1 initiates a transcriptional program that is distinct from that induced by Hog1 and Fus3. Our findings reveal how redundant and shared components coordinate concurrent signals and thereby adapt to sudden environmental changes.
Project description:Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized as progressive and irreversible fibrosis in the interstitium of lung tissues. There is still an unmet need to develop a novel therapeutic drug for IPF. We have previously demonstrated that periostin, a matricellular protein, plays an important role in the pathogenesis of pulmonary fibrosis. However, the underlying mechanism of how periostin causes pulmonary fibrosis remains unclear. In this study, we sought to see whether the cross-talk between transforming growth factor-b (TGF-b), a central mediator in the pathogenesis of pulmonary fibrosis, and periostin in lung fibroblasts leads to generation of pulmonary fibrosis and whether taking advantage of the cross-talk between TGF-b and periostin, inhibitors for integrin aVb3, a periostin receptor, can block pulmonary fibrosis in the model mice. We found that there exists a cross-talk between TGF-b and periostin signals via aVb3/b5 converging into Smad3. This cross-talk is important for expression of several downstream molecules of TGF-b including serpin family E member 1, CCN family member 2/connective tissue growth factor, insulin-like growth factor binding protein-3, and IL-11, all of which have been already shown to be important for pulmonary fibrosis. We, moreover, found several potent integrin inhibitors to block the cross-talking with TGF-b signals and CP4715, one of the compounds, improved bleomycin-induced pulmonary fibrosis in mice. These results suggest that the cross-talk between TGF-b and periostin can be targeted for pulmonary fibrosis and that CP4715 can be a potential therapeutic agent to block the cross-talk between TGF-b and periostin.
Project description:Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized as progressive and irreversible fibrosis in the interstitium of lung tissues. There is still an unmet need to develop a novel therapeutic drug for IPF. We have previously demonstrated that periostin, a matricellular protein, plays an important role in the pathogenesis of pulmonary fibrosis. However, the underlying mechanism of how periostin causes pulmonary fibrosis remains unclear. In this study, we sought to see whether the cross-talk between transforming growth factor-b (TGF-b), a central mediator in the pathogenesis of pulmonary fibrosis, and periostin in lung fibroblasts leads to generation of pulmonary fibrosis and whether taking advantage of the cross-talk between TGF-b and periostin, inhibitors for integrin aVb3, a periostin receptor, can block pulmonary fibrosis in the model mice. We found that there exists a cross-talk between TGF-b and periostin signals via aVb3/b5 converging into Smad3. This cross-talk is important for expression of several downstream molecules of TGF-b including serpin family E member 1, CCN family member 2/connective tissue growth factor, insulin-like growth factor binding protein-3, and IL-11, all of which have been already shown to be important for pulmonary fibrosis. We, moreover, found several potent integrin inhibitors to block the cross-talking with TGF-b signals and CP4715, one of the compounds, improved bleomycin-induced pulmonary fibrosis in mice. These results suggest that the cross-talk between TGF-b and periostin can be targeted for pulmonary fibrosis and that CP4715 can be a potential therapeutic agent to block the cross-talk between TGF-b and periostin.
Project description:Different microbiomes associated with the two copepod species Acartia tonsa and Temora longicornis from the same marine environment
Project description:We describe the molecular cross talk established under in vivo conditions between a set of human gut bifidobacterial commensals. Eleven groups of five conventional female 8-wk-old BALB/c mice taking a standard polysaccharide-rich Chow diet were administered a single daily dose of 109 CFU of either B. bifidum PRL2010, B. breve 12L , B. adolescentis 22L , B. longum subsp. infantis ATCC15697, or bifidobacterial couples, i.e., PRL2010-12L, PRL2010-22L, PRL2010-ATCC15696, 12L-22L, 12L-ATCC15697, 22L-ATCC15697, or a combination of all bifidobacterial strains. The transcriptome of bifidobacterial strains under in vivo conditions was analyzed. The transcripts expressed in B. bifidum PRL2010, B. breve 12L, B. adolescentis 22L and B. longum subsp. infantis ATCC15697 were profiled using a custom-made PRL2010-12L-22L-ATCC15697 (multibifido)-array representing 100%, 99%, 96%, 99% of the identified genes of these organisms, respectively.The observed functional changes in the trascriptomes of bifidobacteria might be caused by the possible shifts of the mice cecum microbiota upon colonization with bifidobacteria. Thus, we assessed if the presence of B. bifidum PRL2010, B. breve 12L, B. adolescentis 22L and B. longum subsp. infantis ATCC15697 on mono-, bi- or multi-association in the cecum of mice affects the overall composition of the microbiota of this environment.
Project description:We describe the molecular cross talk established under in vivo conditions between a set of human gut bifidobacterial commensals. Eleven groups of five conventional female 8-wk-old BALB/c mice taking a standard polysaccharide-rich Chow diet were administered a single daily dose of 109 CFU of either B. bifidum PRL2010, B. breve 12L , B. adolescentis 22L , B. longum subsp. infantis ATCC15697, or bifidobacterial couples, i.e., PRL2010-12L, PRL2010-22L, PRL2010-ATCC15696, 12L-22L, 12L-ATCC15697, 22L-ATCC15697, or a combination of all bifidobacterial strains. The transcriptome of bifidobacterial strains under in vivo conditions was analyzed. The transcripts expressed in B. bifidum PRL2010, B. breve 12L, B. adolescentis 22L and B. longum subsp. infantis ATCC15697 were profiled using a custom-made PRL2010-12L-22L-ATCC15697 (multibifido)-array representing 100%, 99%, 96%, 99% of the identified genes of these organisms, respectively.The observed functional changes in the trascriptomes of bifidobacteria might be caused by the possible shifts of the mice cecum microbiota upon colonization with bifidobacteria. Thus, we assessed if the presence of B. bifidum PRL2010, B. breve 12L, B. adolescentis 22L and B. longum subsp. infantis ATCC15697 on mono-, bi- or multi-association in the cecum of mice affects the overall composition of the microbiota of this environment.
Project description:We describe the molecular cross talk established under in vivo conditions between a set of human gut bifidobacterial commensals. Eleven groups of five conventional female 8-wk-old BALB/c mice taking a standard polysaccharide-rich Chow diet were administered a single daily dose of 109 CFU of either B. bifidum PRL2010, B. breve 12L , B. adolescentis 22L , B. longum subsp. infantis ATCC15697, or bifidobacterial couples, i.e., PRL2010-12L, PRL2010-22L, PRL2010-ATCC15696, 12L-22L, 12L-ATCC15697, 22L-ATCC15697, or a combination of all bifidobacterial strains. The transcriptome of bifidobacterial strains under in vivo conditions was analyzed. The transcripts expressed in B. bifidum PRL2010, B. breve 12L, B. adolescentis 22L and B. longum subsp. infantis ATCC15697 were profiled using a custom-made PRL2010-12L-22L-ATCC15697 (multibifido)-array representing 100%, 99%, 96%, 99% of the identified genes of these organisms, respectively.The observed functional changes in the trascriptomes of bifidobacteria might be caused by the possible shifts of the mice cecum microbiota upon colonization with bifidobacteria. Thus, we assessed if the presence of B. bifidum PRL2010, B. breve 12L, B. adolescentis 22L and B. longum subsp. infantis ATCC15697 on mono-, bi- or multi-association in the cecum of mice affects the overall composition of the microbiota of this environment.