Sehlke, Robert (2019). Integration of molecular regulatory networks: The Drosophila insulin response and mouse embryonic stem cell differentiation dynamics. PhD thesis, Universität zu Köln.
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Abstract
Systems biology relies on considering processes on multiple levels of the organism—e.g. tissues, transcripts and proteins, developmental stages, and age—to generate and test hypotheses that are not amenable to a single-gene approach. This is of particular importance in ageing research, which deals with convoluted relationships between multiple disparate aspects of biology and medicine, as summarized recently in “The Hallmarks of Aging” (López-Otín et al. 2013). In this thesis, I present results from two large collaborative efforts that generated, integrated, and analysed systems level data. These projects focus on two of the nine hallmarks of ageing—deregulated nutrient sensing and stem cell exhaustion—, but touch on several others. The discovery of downstream processes of delayed ageing in Drosophila insulin mutants. This project is further subdivided into four major parts: The tissue-specific proteome response to reduced insulin in the mNSC-ablation model of reduced insulin signalling (IIS). Furthermore, the dependency of these changes on the transcription factor dFOXO. As published in (Tain et al. 2017). The comparison of the tissue-specific proteome responses of mNSC-ablated flies and a second model of reduced IIS, dilp2-3,5 mutant flies. Furthermore, the dependency of the dilp2-3,5 response on the presence of the endosymbiont Wolbachia. The role of post-transcriptional regulation in the tissue-specific proteome to reduced IIS response of dilp2-3,5 mutants, through the analysis of matching RNAseq data. The age-dependent proteome response to reduced IIS in dilp2-3,5 mutants. Presented are preliminary results from two tissues (fat body and thorax). Understanding mouse embryonic stem cell pluripotency and early differentiation. The focus of this project is the analysis of RNAseq data from 74 differentiation defect mESC lines under conditions promoting naive pluripotency or early differentiation. We also present supporting analysis of the specific effect of LIF on naive mESCs and insights from a screen of a inhibitor/knockout screen. As the project is ongoing, results presented in this thesis are preliminary. Additionally, the appendix describes custom R tools that were developed to facilitate the analysis, visualization of results, and collaboration for these projects: CellPlot, SETHRO, and mESCexplorer.
Item Type: | Thesis (PhD thesis) | ||||||||||||||
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URN: | urn:nbn:de:hbz:38-95467 | ||||||||||||||
Date: | 2019 | ||||||||||||||
Language: | English | ||||||||||||||
Faculty: | Faculty of Mathematics and Natural Sciences | ||||||||||||||
Divisions: | CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Außeruniversitäre Forschungseinrichtungen > MPI for Biology of Ageing |
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Subjects: | Data processing Computer science Life sciences |
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Date of oral exam: | 17 May 2018 | ||||||||||||||
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Refereed: | Yes | ||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/9546 |
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