Project description:Ayurvedic drug formulations Bacopa monnieri and Centella asiatica are known to have neuroprotective effects. These have been traditionally used in the treatment of Alzhemeir’s disease, and other neurological deficits. Using pan neuronal Aβ42 model of Drosophila melanogaster, a mass spectrometry based quantitative proteomic analysis platform was used to generate the data on proteins altered in response to the Aβ42 toxicity and restoration of altered proteins by consumption of aqueous extracts of two Ayurvedic drug formulations Bacopa monnieri and Centella asiatica aqueous extract. Quantitative proteomic analysis resulted in 0.67 million mass spectra corresponding to 2,59,168 peptide-spectrum matches (PSM) mapping to 24,305 non- redundant peptides corresponding to 11,480 Drosophila melanogaster proteins. Proteins were filtered for >3 PSMs, resulting in 9,540 proteins. Flies expressing Aβ42 significantly altered 517 proteins which were involved in maintaining essential neuronal functions. Supplementing flies with Bacopa monnieri or Centella asiatica extract commonly rescued 224 proteins from Aβ42 toxicity, moreover, extract supplemented group significantly altered proteins which were additionally supporting neuronal maintenance in flies with Aβ42 stress.
Project description:Understanding the genotype-phenotype map and how variation at different levels of biological organization is associated are central topics in modern biology. Fast developments in sequencing technologies and other molecular omic tools enable researchers to obtain detailed information on variation at DNA level and on intermediate endophenotypes, such as RNA, proteins and metabolites. This can facilitate our understanding of the link between genotypes and molecular and functional organismal phenotypes. Here, we use the Drosophila melanogaster Genetic Reference Panel and nuclear magnetic resonance (NMR) metabolomics to investigate the ability of the metabolome to predict organismal phenotypes. We performed NMR metabolomics on four replicate pools of male flies from each of 170 different isogenic lines. Our results show that metabolite profiles are variable among the investigated lines and that this variation is highly heritable. Second, we identify genes associated with metabolome variation. Third, using the metabolome gave better prediction accuracies than genomic information for four of five quantitative traits analyzed. Our comprehensive characterization of population-scale diversity of metabolomes and its genetic basis illustrates that metabolites have large potential as predictors of organismal phenotypes. This finding is of great importance, e.g., in human medicine, evolutionary biology and animal and plant breeding.
Project description:Nucleus is a highly structured organelle and contains many functional compartments. While the structural basis for this complex spatial organization of compartments is unknown, a major component of this organization is likely to be the non-chromatin scaffolding called nuclear matrix (NuMat). Experimental evidence over the past decades indicates that most of the nuclear functions are at least transiently associated with the NuMat although the components of NuMat itself are poorly known. Here, we report NuMat proteome analysis from Drosophila melanogaster embryos and discuss its links with nuclear architecture and functions. In the NuMat proteome, we find structural proteins, chaperones related, DNA/RNA binding, chromatin remodeling and transcription factors. This complexity of NuMat proteome is an indicator of its structural and functional significance. Comparison of the 2D profile of NuMat proteome from different developmental stages of Drosophila embryos shows that less than half of the NuMat proteome is constant and rest of the proteins are stage specific dynamic components. This NuMat dynamics suggests a possible functional link between NuMat and the embryonic development. Finally, we also show that a subset of NuMat proteins remain associated with the mitotic chromosomes implicating their role in mitosis and possibly the epigenetic cellular memory. NuMat proteome analysis provides tools and opens up ways to understand nuclear organization and function.