6482 2012 eng article 1 2013-03-16 -- -- Integrated pathway modules using time-course metabolic profiles and EST data from Milnesium tardigradum Background: Tardigrades are multicellular organisms, resistant to extreme environmental changes such as heat, drought, radiation and freezing. They outlast these conditions in an inactive form (tun) to escape damage to cellular structures and cell death. Tardigrades are apparently able to prevent or repair such damage and are therefore a crucial model organism for stress tolerance. Cultures of the tardigrade Milnesium tardigradum were dehydrated by removing the surrounding water to induce tun formation. During this process and the subsequent rehydration, metabolites were measured in a time series by GC-MS. Additionally expressed sequence tags are available, especially libraries generated from the active and inactive state. The aim of this integrated analysis is to trace changes in tardigrade metabolism and identify pathways responsible for their extreme resistance against physical stress. Results: In this study we propose a novel integrative approach for the analysis of metabolic networks to identify modules of joint shifts on the transcriptomic and metabolic levels. We derive a tardigrade-specific metabolic network represented as an undirected graph with 3,658 nodes (metabolites) and 4,378 edges (reactions). Time course metabolite profiles are used to score the network nodes showing a significant change over time. The edges are scored according to information on enzymes from the EST data. Using this combined information, we identify a key subnetwork (functional module) of concerted changes in metabolic pathways, specific for de- and rehydration. The module is enriched in reactions showing significant changes in metabolite levels and enzyme abundance during the transition. It resembles the cessation of a measurablemetabolism (e.g. glycolysis and amino acid anabolism) during the tun formation, the production of storage metabolites and bioprotectants, such as DNA stabilizers, and the generation of amino acids and cellular components from monosaccharides as carbon and energy source during rehydration. Conclusions: The functional module identifies relationships among changed metabolites (e.g. spermidine) and reactions and provides first insights into important altered metabolic pathways. With sparse and diverse data available, the presented integrated metabolite network approach is suitable to integrate all existing data and analyse it in a combined manner. urn:nbn:de:bvb:20-opus-75241 7524 In: BMC Systems Biology (2012) 6: 72, doi:10.1186/1752-0509-6-72 Daniela Beisser Markus A. Grohme Joachim Kopka Marcus Frohme Ralph O. Schill Steffen Hengherr Thomas Dandekar Gunnar W. Klau Marcus Dittrich Tobias Müller deu swd Milnesium tardigradum eng uncontrolled Integrated network analysis eng uncontrolled Functional modules eng uncontrolled Metabolic profiles eng uncontrolled Metabolic pathways eng uncontrolled Trend test Biowissenschaften; Biologie open_access Theodor-Boveri-Institut für Biowissenschaften Förderzeitraum 2012 Universität Würzburg https://opus.bibliothek.uni-wuerzburg.de/files/6482/019_1752_0509_6_72.pdf 12308 2012 eng 69-96 6 article 1 2015-12-14 -- -- Transcriptome analysis in tardigrade species reveals specific molecular pathways for stress adaptations Tardigrades have unique stress-adaptations that allow them to survive extremes of cold, heat, radiation and vacuum. To study this, encoded protein clusters and pathways from an ongoing transcriptome study on the tardigrade \(Milnesium\) \(tardigradum\) were analyzed using bioinformatics tools and compared to expressed sequence tags (ESTs) from \(Hypsibius\) \(dujardini\), revealing major pathways involved in resistance against extreme environmental conditions. ESTs are available on the Tardigrade Workbench along with software and databank updates. Our analysis reveals that RNA stability motifs for \(M.\) \(tardigradum\) are different from typical motifs known from higher animals. \(M.\) \(tardigradum\) and \(H.\) \(dujardini\) protein clusters and conserved domains imply metabolic storage pathways for glycogen, glycolipids and specific secondary metabolism as well as stress response pathways (including heat shock proteins, bmh2, and specific repair pathways). Redox-, DNA-, stress- and protein protection pathways complement specific repair capabilities to achieve the strong robustness of \(M.\) \(tardigradum\). These pathways are partly conserved in other animals and their manipulation could boost stress adaptation even in human cells. However, the unique combination of resistance and repair pathways make tardigrades and \(M.\) \(tardigradum\) in particular so highly stress resistant. Bioinformatics and biology insights PMC3342025 10.4137/BBI.S9150 urn:nbn:de:bvb:20-opus-123089 This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited. Bioinformatics and Biology Insights 2012:6 69–96. doi: 10.4137/BBI.S9150 Frank Förster Daniela Beisser Markus A. Grohme Chunguang Liang Brahim Mali Alexander Matthias Siegl Julia C. Engelmann Alexander V. Shkumatov Elham Schokraie Tobias Müller Martina Schnölzer Ralph O. Schill Marcus Frohme Thomas Dandekar eng uncontrolled RNA eng uncontrolled expressed sequence tag eng uncontrolled cluster eng uncontrolled protein familiy eng uncontrolled adaption eng uncontrolled tardigrada eng uncontrolled transcriptome Biowissenschaften; Biologie open_access Theodor-Boveri-Institut für Biowissenschaften Universität Würzburg https://opus.bibliothek.uni-wuerzburg.de/files/12308/f_3147-BBI-Transcriptome-Analysis-in-Tardigrade-Species-Reveals-Specific-Molecula.pdf_4261.pdf 13444 2012 eng e45682 9 7 article 1 2016-06-06 -- -- Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state Tardigrades have fascinated researchers for more than 300 years because of their extraordinary capability to undergo cryptobiosis and survive extreme environmental conditions. However, the survival mechanisms of tardigrades are still poorly understood mainly due to the absence of detailed knowledge about the proteome and genome of these organisms. Our study was intended to provide a basis for the functional characterization of expressed proteins in different states of tardigrades. High-throughput, high-accuracy proteomics in combination with a newly developed tardigrade specific protein database resulted in the identification of more than 3000 proteins in three different states: early embryonic state and adult animals in active and anhydrobiotic state. This comprehensive proteome resource includes protein families such as chaperones, antioxidants, ribosomal proteins, cytoskeletal proteins, transporters, protein channels, nutrient reservoirs, and developmental proteins. A comparative analysis of protein families in the different states was performed by calculating the exponentially modified protein abundance index which classifies proteins in major and minor components. This is the first step to analyzing the proteins involved in early embryonic development, and furthermore proteins which might play an important role in the transition into the anhydrobiotic state. PLoS One 10.1371/journal.pone.0045682 urn:nbn:de:bvb:20-opus-134447 PLoS ONE 7(9): e45682. doi:10.1371/journal.pone.0045682 Elham Schokraie Uwe Warnken Agnes Hotz-Wagenblatt Markus A. Grohme Steffen Hengherr Frank Förster Ralph O. Schill Marcus Frohme Thomas Dandekar Martina Schnölzer eng uncontrolled life-span regulation eng uncontrolled genes eng uncontrolled Yolk protein eng uncontrolled water stress eng uncontrolled expression eng uncontrolled tolerance eng uncontrolled richtersius coronifer eng uncontrolled superoxide-dismutase eng uncontrolled caenorhabditis elegans eng uncontrolled arabidopsis thaliana eng uncontrolled vitellogenin Datenverarbeitung; Informatik Biowissenschaften; Biologie open_access Theodor-Boveri-Institut für Biowissenschaften Universität Würzburg https://opus.bibliothek.uni-wuerzburg.de/files/13444/Schokraie_PLoSOne.pdf