Nikolaus Sonnenschein

• The thesis presented here is summarizing and interconnecting a series of articles on the network organization of metabolic and gene regulatory processes. These publications are the product of my PhD work. They cover the following scientific questions: (i) Does the spatial distribution of genes on a chromosome deviate from randomness, and if so, does it contribute to the transcriptional regulation of genes? (ii) Is the transcriptional regulation of metabolic processes predominantly accomplished by the classically conceived form of control that is exerted by the digital actions of transcription factors, or does the homeostatic control of chromosome and chromatin structure play a significant role, which is an analog type of regulation? (iii) Is it generally possible to quantify the impact of perturbations to the regulatory machinery and environment of an organism by the integration of gene expression profiles and genome-scale metabolic reconstructions? (iv) Can we assign topological markers to different forms of perturbations in the systems under investigation, e.g., the medium-dependent essentiality of reactions or metabolically altered system states in cancer cells? An introduction to these topics is provided in the first part of this thesis. In addition, concluding remarks and a future outlook will be given at the end of the thesis.