Quantitative data on the dynamic changes in the transcriptome and the metabolome of yeast in resp... more Quantitative data on the dynamic changes in the transcriptome and the metabolome of yeast in response to an impulse-like perturbation in nutrient availability was integrated with the metabolic pathway information in order to elucidate the long-term dynamic re-organization of the cells. This study revealed that, in addition to the dynamic re-organization of the de novo biosynthetic pathways, salvage pathways were also re-organized in a time-dependent manner upon catabolite repression. The transcriptional and the metabolic responses observed for nitrogen catabolite repression were not as severe as those observed for carbon catabolite repression. Selective up-or down regulation of a single member of a paralogous gene pair during the response to the relaxation from nutritional limitation was identified indicating a differentiation of functions among paralogs. Our study highlighted the role of inosine accumulation and recycling in energy homeostasis and indicated possible bottlenecks in the process.
Dupuytren's disease (DD) is an ill-defined fibroproliferative disorder affecting the palm of the ... more Dupuytren's disease (DD) is an ill-defined fibroproliferative disorder affecting the palm of the hand, resulting in progressive and irreversible digital contracture. In view of the abnormal gene dysregulation found in DD, and its potential effect on metabolites at a functional level, we chose to examine the metabolic profile involved in DD. Using Fourier transform infrared (FT-IR) spectroscopy to generate metabolic fingerprints of cultured cells, we compared the profiles of DD cords and nodules (1) against the unaffected transverse palmar fascia (internal control), (2) against carpal ligamentous fascia (external control), and (3) against fibroblasts from fat surrounding the nodule and skin overlying the nodule (environmental control). We also determined the effects of serial passaging of the cells on DD fingerprints. Subsequently, gas chromatographymass spectrometry (GC-MS) was employed for metabolic profiling in order to identify metabolites characteristic of the DD tissue phenotypes. We developed a robust metabolomic analysis procedure of DD using cultured fibroblasts derived from DD tissues. Our carefully controlled culture conditions, combined with assessment of metabolic phenotypes by FT-IR and GC-MS, enabled us to demonstrate metabolic differences between DD and unaffected transverse palmar fascia and between DD and healthy control tissue. In early passage (0-3) the metabolic differences were clear, but cells from subsequent passages (4-6) started to lose this distinction between diseased and non-diseased origen. The dysregulated metabolites we identified were leucine, phenylalanine, lysine, cysteine, aspartic acid, glycerol-3-phosphate and the vitamin precursor to coenzyme A. Early passage DD cells exhibit a clear metabolic profile, in which central metabolic pathways appear to be involved. Experimental conditions have been identified in which these DD data are reproducible. The experimental reproducibility will be useful in DD diagnostics and for DD systems biology.
Quantitative data on the dynamic changes in the transcriptome and the metabolome of yeast in resp... more Quantitative data on the dynamic changes in the transcriptome and the metabolome of yeast in response to an impulse-like perturbation in nutrient availability was integrated with the metabolic pathway information in order to elucidate the long-term dynamic re-organization of the cells. This study revealed that, in addition to the dynamic re-organization of the de novo biosynthetic pathways, salvage pathways were also re-organized in a time-dependent manner upon catabolite repression. The transcriptional and the metabolic responses observed for nitrogen catabolite repression were not as severe as those observed for carbon catabolite repression. Selective up-or down regulation of a single member of a paralogous gene pair during the response to the relaxation from nutritional limitation was identified indicating a differentiation of functions among paralogs. Our study highlighted the role of inosine accumulation and recycling in energy homeostasis and indicated possible bottlenecks in the process.
Dupuytren's disease (DD) is an ill-defined fibroproliferative disorder affecting the palm of the ... more Dupuytren's disease (DD) is an ill-defined fibroproliferative disorder affecting the palm of the hand, resulting in progressive and irreversible digital contracture. In view of the abnormal gene dysregulation found in DD, and its potential effect on metabolites at a functional level, we chose to examine the metabolic profile involved in DD. Using Fourier transform infrared (FT-IR) spectroscopy to generate metabolic fingerprints of cultured cells, we compared the profiles of DD cords and nodules (1) against the unaffected transverse palmar fascia (internal control), (2) against carpal ligamentous fascia (external control), and (3) against fibroblasts from fat surrounding the nodule and skin overlying the nodule (environmental control). We also determined the effects of serial passaging of the cells on DD fingerprints. Subsequently, gas chromatographymass spectrometry (GC-MS) was employed for metabolic profiling in order to identify metabolites characteristic of the DD tissue phenotypes. We developed a robust metabolomic analysis procedure of DD using cultured fibroblasts derived from DD tissues. Our carefully controlled culture conditions, combined with assessment of metabolic phenotypes by FT-IR and GC-MS, enabled us to demonstrate metabolic differences between DD and unaffected transverse palmar fascia and between DD and healthy control tissue. In early passage (0-3) the metabolic differences were clear, but cells from subsequent passages (4-6) started to lose this distinction between diseased and non-diseased origen. The dysregulated metabolites we identified were leucine, phenylalanine, lysine, cysteine, aspartic acid, glycerol-3-phosphate and the vitamin precursor to coenzyme A. Early passage DD cells exhibit a clear metabolic profile, in which central metabolic pathways appear to be involved. Experimental conditions have been identified in which these DD data are reproducible. The experimental reproducibility will be useful in DD diagnostics and for DD systems biology.
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Papers by Warwick Dunn