Project description:Proteomic and Metabolomic analysis of exercise-induced sweat to evaluate analyte correlation with human performance parameters. Sweat was collected from participants on a treadmill at low, medium, and hard speed and incline. Sweat was analyzed by untagged HILIC LC-MS.
Project description:Gene expression microarrays accompanying "Proteomic and genomic characterization of a yeast model for Ogden syndrome" by Doerfel et al 2016 in press at Yeast. Naa10 is a Na-terminal acetyltransferase that, in a complex with its auxiliary subunit Naa15, co-translationally acetylates the a-amino group of newly synthetized proteins as they emerge from the ribosome. Roughly 40-50% of the human proteome is acetylated by Naa10, rendering this an enzyme with one of the most broad substrate ranges known. Recently, we reported an X-linked disorder of infancy, Ogden syndrome, in two families harboring a c.109T>C (p.Ser37Pro) variant in NAA10. In the present study we performed in-depth characterization of a yeast model of Ogden syndrome. Stress tests and proteomic analyses suggest that the S37P mutation disrupts Naa10 function and reduces cellular fitness during heat shock, possibly due to dysregulation of chaperone expression and accumulation. Microarray and RNA-seq revealed a pseudo-diploid gene expression profile in DNaa10 cells, likely responsible for a mating defect. In conclusion, the data presented here further support the disruptive nature of the S37P/Ogden mutation and identify affected cellular processes potentially contributing to the severe phenotype seen in Ogden syndrome.
Project description:The pathophysiological effects of a number of metabolic and age-related disorders can be prevented to some extent by exercise and increased physical activity. However, the molecular mechanisms that contribute to the beneficial effects of muscle activity remain poorly explored. Availability of a fast, inexpensive, and genetically tractable model for muscle activity and exercise will allow rapid identification and characterization of the molecular mechanisms that mediate the beneficial effects of muscle activity. Here, we report the development and characterization of an optogenetically-inducible muscle contraction (OMC) model in Drosophila larvae that we used to model acute exercise-like physiological responses. To characterize muscle-specific transcriptional responses to acute exercise, we performed bulk mRNA-sequencing, revealing striking similarities between acute exercise-induced genes in flies and those previously identified in humans. Our larval muscle contraction model opens a path for rapid identification and characterization of exercise-induced factors.
Project description:Fish species display huge differences in physical activity ranging from lethargy to migration of thousands of miles, making them an interesting model for human exercise. Here, we show a remarkable plasticity of zebrafish in response to exercise and induction of PGC1α (encoded by PPARGC1A), a dominant regulator of mitochondrial biogenesis. Forced expression of human PPARGC1A induces mitochondrial biogenesis, an exercise-like gene expression signature, and physical fitness comparable to wild-type animals trained in counter-current swim tunnels. We quantify a stoichiometric induction of the electron transport chain (ETC) in response to exercise or PGC1α expression, identified by a proteomic SWATH-MS workflow. Exercise or PGC1α expression induce the re-organization of the ETC into respiratory supercomplexes, and we show that ndufa4/ndufa4l, previously assigned to complex I, associates to free and supramolecular complex IV in vivo. Thus, zebrafish is a useful and experimentally tractable vertebrate model to study exercise biology, including ETC expression and assembly.
Project description:Naa10 is a Nα-terminal acetyltransferase that, in a complex with its auxiliary subunit Naa15, co-translationally acetylates the α-amino group of newly synthetized proteins as they emerge from the ribosome. Roughly 40-50% of the human proteome is acetylated by Naa10, rendering this an enzyme with one of the most broad substrate ranges known. Recently, we reported an X-linked disorder of infancy, Ogden syndrome, in two families harboring a c.109T>C (p.Ser37Pro) variant in NAA10. In the present study we performed in-depth characterization of a yeast model of Ogden syndrome. Stress tests and proteomic analyses suggest that the S37P mutation disrupts Naa10 function and reduces cellular fitness during heat shock, possibly due to dysregulation of chaperone expression and accumulation. Microarray and RNA-seq revealed a pseudo-diploid gene expression profile in ΔNaa10 cells, likely responsible for a mating defect. In conclusion, the data presented here further support the disruptive nature of the S37P/Ogden mutation and identify affected cellular processes potentially contributing to the severe phenotype seen in Ogden syndrome.
Project description:To gain insight into the mechanisms by which exercise affects hematopoietic stem cells, we subjected young and old mice to aerobic exercise and performed single cell transcriptome analysis of hematopoietic progenitors in the bone marrow of these animals.
Project description:The effect of exercise on human metabolism is obvious. However, the effect of chronic exercise on liver metabolism in mice is less well described. The healthy adult mice running for 6 weeks as exercise model and sedentary mice as control were used to perform transcriptomic, proteomic, acetyl-proteomics, and metabolomics analysis. In addition, correlation analysis between transcriptome and proteome, and proteome and metabolome was conducted as well. This dataset is transcriptomic data.