TY - THES A1 - Steinhauser, Dirk T1 - Inferring hypotheses from complex profile data - by means of CSB.DB, a comprehensive systems-biology database T1 - Generierung von Hypothesen aus komplexen Profildaten mittels CSB.DB, a comprehensive systems-biology database N2 - The past decades are characterized by various efforts to provide complete sequence information of genomes regarding various organisms. The availability of full genome data triggered the development of multiplex high-throughput assays allowing simultaneous measurement of transcripts, proteins and metabolites. With genome information and profiling technologies now in hand a highly parallel experimental biology is offering opportunities to explore and discover novel principles governing biological systems. Understanding biological complexity through modelling cellular systems represents the driving force which today allows shifting from a component-centric focus to integrative and systems level investigations. The emerging field of systems biology integrates discovery and hypothesis-driven science to provide comprehensive knowledge via computational models of biological systems. Within the context of evolving systems biology, investigations were made in large-scale computational analyses on transcript co-response data through selected prokaryotic and plant model organisms. CSB.DB - a comprehensive systems-biology database - (http://csbdb.mpimp-golm.mpg.de/) was initiated to provide public and open access to the results of biostatistical analyses in conjunction with additional biological knowledge. The database tool CSB.DB enables potential users to infer hypothesis about functional interrelation of genes of interest and may serve as future basis for more sophisticated means of elucidating gene function. The co-response concept and the CSB.DB database tool were successfully applied to predict operons in Escherichia coli by using the chromosomal distance and transcriptional co-responses. Moreover, examples were shown which indicate that transcriptional co-response analysis allows identification of differential promoter activities under different experimental conditions. The co-response concept was successfully transferred to complex organisms with the focus on the eukaryotic plant model organism Arabidopsis thaliana. The investigations made enabled the discovery of novel genes regarding particular physiological processes and beyond, allowed annotation of gene functions which cannot be accessed by sequence homology. GMD - the Golm Metabolome Database - was initiated and implemented in CSB.DB to integrated metabolite information and metabolite profiles. This novel module will allow addressing complex biological questions towards transcriptional interrelation and extent the recent systems level quest towards phenotyping. N2 - Die vergangenen Jahrzehnte waren gekennzeichnet durch umfangreiche Bemühungen, die Genomsequenz verschiedener Organismen vollständig zu entschlüsseln. Die Verfügbarkeit vollständiger genomischer Daten löste die Entwicklung von modernen Hochdurchsatzmethoden aus, welche die gleichzeitige Messung von verschiedenen Transkripten, Proteinen und Metaboliten erlauben. Mittels genomischer Informationen und Hochdurchsatztechnologien erlaubt eine hoch parallelisierte experimentelle Biologie die Erforschung von Gesetzmäßigkeiten, welchen biologischen Systemen zugrunde liegen. Das Verständnis biologischer Komplexität durch Modellierung zellulärer Systeme repräsentiert die treibende Kraft, welche heutzutage den Element-zentrierten Focus auf integrative und ganzheitliche Untersuchungen lenkt. Das sich entwickelnde Feld der Systembiologie integriert Entdeckungs- und Hypothesen-getriebene Wissenschaft um ein umfangreiches Wissen durch Computermodelle biologischer Systeme bereitzustellen. Im Kontext der sich neu entwickelnden Systembiologie investierte ich in umfangreiche Computeranalysen zur Transkript Co-Response bezüglich ausgewählter prokaryotischer und pflanzlicher eukaryotischer Organismen. CSB.DB - a comprehensive systems-biology database - (http://csbdb.mpimp-golm.mpg.de/) wurde initiiert, um freien Zugang zu den biostatistischen Ergebnissen als auch zu weiterem biologischem Wissen zu bieten. Die Datenbank CSB.DB ermöglicht potentiellen Anwendern die Hypothesengenerierung bezüglich der funktionalen Wechselbeziehungen von Genen von Interesse und kann zukünftig die Grundlage für einen fortgeschrittenen Weg der Zuordnung von Genfunktionen darstellen. Unter Verwendung chromosomaler Distanzen und Transkript Co-Response konnte das Konzept und CSB.DB angewandt werden, um bakterielle Operons in Escherichia coli erfolgreich vorherzusagen. Darüber hinaus werden Beispiele gezeigt, die andeuten, dass die Transkript Co-Response Analyse eine Identifizierung differentieller Promoteraktivität in verschiedenen experimentellen Bedingungen ermöglicht. Das Co-Response Konzept wurde, mit dem Schwerpunkt auf die eukaryotische Modellpflanze Arabidopsis thaliana, erfolgreich auf komplexere Organismen angewandt. Die durchgeführten Untersuchungen ermöglichten die Identifizierung neuer Gene hinsichtlich physiologischer Prozesse und darüber hinaus die Zuweisung von Genfunktionen, welche nicht durch Sequenzhomologie ermöglicht werden kann. GMD - The Golm Metabolome Database - wurde initiiert und in CSB.DB implementiert, um Metaboliten Informationen als auch Metaboliten Profile zu integrieren. Dieses neue Modul ermöglicht die Ausrichtung auf komplexere biologische Fragen und erweitert die derzeitige systembiologische Fragestellung in Richtung Phänotypus-Zuordnung. T2 - Inferring hypotheses from complex profile data - by means of CSB.DB, a comprehensive systems-biology database KW - Datenbank KW - Korrelation KW - Korrelationsanalyse KW - Escherichia coli KW - Saccharomyces cerevisiae KW - Ackerschmalwand KW - Operon KW - Brassinosteroide KW - Transkript KW - database KW - correlation KW - co-response KW - metabolite KW - transcript Y1 - 2004 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-2467 ER - TY - JOUR A1 - Jüppner, Jessica A1 - Mubeen, Umarah A1 - Leisse, Andrea A1 - Caldana, Camila A1 - Brust, Henrike A1 - Steup, Martin A1 - Herrmann, Marion A1 - Steinhauser, Dirk A1 - Giavalisco, Patrick T1 - Dynamics of lipids and metabolites during the cell cycle of Chlamydomonas reinhardtii JF - The plant journal N2 - Metabolites and lipids are the final products of enzymatic processes, distinguishing the different cellular functions and activities of single cells or whole tissues. Understanding these cellular functions within a well-established model system requires a systemic collection of molecular and physiological information. In the current report, the green alga Chlamydomonas reinhardtii was selected to establish a comprehensive workflow for the detailed multi-omics analysis of a synchronously growing cell culture system. After implementation and benchmarking of the synchronous cell culture, a two-phase extraction method was adopted for the analysis of proteins, lipids, metabolites and starch from a single sample aliquot of as little as 10-15million Chlamydomonas cells. In a proof of concept study, primary metabolites and lipids were sampled throughout the diurnal cell cycle. The results of these time-resolved measurements showed that single compounds were not only coordinated with each other in different pathways, but that these complex metabolic signatures have the potential to be used as biomarkers of various cellular processes. Taken together, the developed workflow, including the synchronized growth of the photoautotrophic cell culture, in combination with comprehensive extraction methods and detailed metabolic phenotyping has the potential for use in in-depth analysis of complex cellular processes, providing essential information for the understanding of complex biological systems. KW - Chlamydomonas reinhardtii KW - synchronized cell cultures KW - photoautotrophic growth KW - cell cycle KW - metabolomics KW - lipidomics KW - systems biology KW - two-phase extraction KW - diurnal cycle KW - technical advance Y1 - 2017 U6 - https://doi.org/10.1111/tpj.13642 SN - 0960-7412 SN - 1365-313X VL - 92 SP - 331 EP - 343 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Meissner, Sven A1 - Steinhauser, Dirk A1 - Dittmann-Thünemann, Elke T1 - Metabolomic analysis indicates a pivotal role of the hepatotoxin microcystin in high light adaptation of Microcystis JF - Environmental microbiology N2 - Microcystis is a freshwater cyanobacterium frequently forming nuisance blooms in the summer months. The genus belongs to the predominant producers of the potent hepatotoxin microcystin. The success of Microcystis and its remarkable resistance to high light conditions are not well understood. Here, we have compared the metabolic response of Microcystis aeruginosaPCC7806, its microcystin-deficient mcyB mutant (Mut) and the cyanobacterial model organism SynechocystisPCC6803 to high light exposure of 250molphotonsm(-2)s(-1) using GC/MS-based metabolomics. Microcystis wild type and Mut show pronounced differences in their metabolic reprogramming upon high light. Seventeen percent of the detected metabolites showed significant differences between the two genotypes after high light exposure. Whereas the microcystin-producing wild type shows a faster accumulation of glycolate upon high light illumination, loss of microcystin leads to an accumulation of general stress markers such as trehalose and sucrose. The study further uncovers differences in the high light adaptation of the bloom-forming cyanobacterium Microcystis and the model cyanobacterium Synechocystis. Most notably, Microcystis invests more into carbon reserves such as glycogen after high light exposure. Our data shed new light on the lifestyle of bloom-forming cyanobacteria, the role of the widespread toxin microcystin and the metabolic diversity of cyanobacteria. Y1 - 2015 U6 - https://doi.org/10.1111/1462-2920.12565 SN - 1462-2912 SN - 1462-2920 VL - 17 IS - 5 SP - 1497 EP - 1509 PB - Wiley-Blackwell CY - Hoboken ER -