Universität Stuttgart
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Item Open Access Mechanistic studies on the DNA methyltransferases DNMT3A and DNMT3B(2021) Dukatz, Michael; Jeltsch, Albert (Prof. Dr.)In this work, both regulatory and catalytic mechanisms of de novo methyltransferases were investigated, which include interactions with other proteins and the specific recognition of the substrate sequence. Another part of this work strived to elucidate how enzymatic generation of 3-methylcytosine by DNMT3A can occur.Item Open Access Studien zur biotechnologischen Anwendung und ökologischen Funktion von Pyrrolochinolinchinon(PQQ)-abhängigen Alkoholdehydrogenasen(2021) Wehrmann, Matthias; Hauer, Bernhard (Prof. Dr.)Item Open Access Molecular dynamics simulations of the substrate- and product specificity and mechanism of DNA- and protein lysine methyltransferases(2024) Schnee, Philipp; Jeltsch, Albert (Prof. Dr.)Protein Lysine Methyltransferases (PKMTs) regulate the epigenetic code of cells and their alteration via somatic mutations are often associated with cancer. The aim of this project is to rationalize the product and substrate specificity of this enzyme family by a combination of biochemical experiments and molecular dynamics simulations. Based on this, a detailed view of the underlying mechanism behind the disease associated mutations shall be gained, which may provide new possibilities for personalized cancer therapies.Item Open Access Development and application of fluorescent reporter assays for the investigation of chromatin regulation(2021) Pinter, Sabine; Jeltsch, Albert (Prof. Dr.)Item Open Access Allele-specific epigenome editing : development and clinical application(2024) Kouroukli, Alexandra; Jeltsch, Albert (Prof. Dr.)Item Open Access EPIC’RISPR: a modular and inducible platform for highly parallel synthetic epigenetics and chromatin imaging in a high-throughput format(2021) Oberacker, Phil; Jurkowski, Tomasz P. (Dr.)The epigenome describes the sum of epigenetic states in an organism. It consists of biochemical modifications of the DNA and histone proteins, non-coding RNAs and the three-dimensional architecture of the genome. These modifications and structures regulate the genome expression in a cell-type-specific pattern and hence control the development of the whole organism. Research in this field yielded a lot of descriptive information about the correlation between epigenetic marks and gene expression. Unfortunately, we do not know much about the causalities within the epigenetic network. With the discovery of the groundbreaking CRISPR/Cas9 technology, it is now possible to interfere with the epigenetic program. This methodology, which is known as epigenetic editing, allows the recruitment of effector molecules to distinct targets where they introduce or remove specific modifications. By observing the response of the epigenome, we can conclude how the epigenetic network functions. However, this system is somewhat limited regarding the simultaneous modification of multiple loci, which is a necessity for investigating a network. In this thesis, I combined the targeting and recruiting functionality of the CRISPR/Cas9 system in one molecule, the gRNA. Like this, this EPIC’RISPR platform can recruit numerous effector molecules to one or multiple targets simultaneously without interference. I demonstrated this by activating and repressing three target genes with different effector domains at once and by recruiting different fluorophores to several target loci. I further applied this technology to perturb five differently expressed target genes simultaneously with one effector molecule at a time. For this, I performed a large-scale experiment in which I probed the effects of more than 60 epigenetic effector molecules on target gene transcription. I identified several promising candidates which might exhibit synergistic behaviour and hence a stronger and longer-lasting impact on the epigenetic program. Furthermore, I developed ON- and OFF-switches for the EPIC’RISPR system which utilize small molecules to fine-tune the introduced effects arbitrarily. The OFF-switch was further applied for transgene expression control, extending the functionality of this system even further. Additionally, our group developed protocols for the synthesis and functionalisation of paramagnetic beads and their application in the automated high-throughput extraction of nucleic acids. Since its publication, our platform, which we call Bio-On-Magnetic-Beads (BOMB) has since become a hub for collaborations in open-source science, especially during the COVID-19 pandemic.Item Open Access Mechanistic study on the DNA methyltransferase DNMT3A(2024) Kunert, Stefan; Jeltsch, Albert (Prof. Dr.)Item Open Access Squalene-Hopene cyclase catalyzed isomerization of monoterpenes(2020) Diether, Svenja; Hauer, Bernhard (Prof. Dr.)Item Open Access Novel approaches to investigate the cellular effects of epigenome modifications(2024) Köhler, Anja R.; Jeltsch, Albert (Prof. Dr.)Item Open Access Peptide und Fusionsproteine für die Biomineralisation von Hydroxylapatit(2021) Henkes, Thorsten Matthias; Hauer, Bernhard (Prof. Dr.)Mittels des sogenannten Phagen Display wurden Peptide identifiziert, welche an Hydroxylapatit binden. Diese Bindemotive wurden in oberflächenaktive Fusionsproteine integriert. Die Bindung der Phagen-präsentierten Peptide, von synthetischen Peptiden und der Fusionsproteine an Hydroxylapatit sowie der Einfluss von Peptiden und Fusionsproteinen auf die Nukleation von Hydroxylapatit wurden untersucht. Ebenso wurden gebildete Präzipitate mittels SEM EDX und TEM charakterisiert. Auf diese Weise wurden Peptidmotive und Fusionsproteine identifiziert, welche die Nukleation von Hydroxylapatit beschleunigen oder verlangsamen können.