Dates and Events

• Prof. Jörg Stülke, University of Göttingen: Microbial nucleotide metabolism: News from Bacillus subtilis Speaker Series. The Stülke lab studies the regulation of metabolism in the pathogenic bacterium Mycoplasma pneumoniae and the model organism Bacillus subtilis. They are following global (“post-genomic”) and gene-specific approaches. In Bacillus subtilis, metabolism is studied by transcriptomics, metabolome and fluxome analyses. The specific interests are focussed on two key pathways: glycolysis and glutamate biosynthesis, the decisive link between carbon and nitrogen metabolism. The regulation of glycolysis is studied at the level of a controlled protein-RNA interaction. Regulation through RNA has become widely recognized in the past few years. The lab’s studies revealed that glycolytic enzymes themselves are part of a protein complex that is required for mRNA processing and degradation. Interest is also directed at systems biology approaches to the analysis of B. subtilis and the development of web interfaces for the functional annotation.
• Dr. Patricia Bedrunka: New insights into the regulatory networks of Bacillus subtilis controlling biofilm formation and cell motility PI Lecture
• Prof. Andrea Rentmeister, Ludwig-Maximilians-Universität München: Harnessing Click Chemistry and Light for Precise Analysis and Control of mRNA Speaker Series. Messenger RNAs (mRNAs) enable the production of almost any functional protein/peptide in the human body as a vaccine or therapeutic agent. The translation of mRNA is a fundamental process in gene expression, and controlling translation is crucial for regulating the production of proteins in cells. In addition, internal modifications of mRNA have emerged as widespread and versatile regulatory mechanism to control gene expression at the post-transcriptional level. Most of these modifications are methyl groups, making S-adenosyl-L-methionine (SAM) a central metabolic hub. We established metabolic labeling with a clickable metabolic precursor of SAM that enables detection and identification of various methylation sites. Integration into next generation sequencing enabled mapping of N6-methyladenosine (m6A) and 5-methylcytidine (m5C) sites in mRNA with single nucleotide precision and independent of antibodies. In a different project, we aimed to control translation of mRNA by light as external stimulus. We synthesized 5′ cap analogues with photo-cleavable groups (FlashCaps) that prohibit binding to the eukaryotic translation initiation factor eIF4E. These compounds are compatible with the general and efficient production of mRNAs by in vitro transcription. FlashCaps offer a route to regulate the expression of any given mRNA in vitro and in cells and may provide an approach to dose mRNA therapeutics with spatio-temporal control.
• Prof. Aurelio Teleman, German Cancer Research Center, Heidelberg: Non-uniform regulation of epigenetic marks via metabolism in a developing tissue Speaker Series. Abstract: Histone acetylation regulates gene expression, cell function, and cell fate. We studied the pattern of histone acetylation in an epithelial tissue, the Drosophila wing disc and find that H3K18ac, H4K8ac, and total lysine acetylation are elevated in the outer rim of the disc. This is due in part to high fatty acid β-oxidation (FABO) in the rim, and partly due to nuclear positioning. This affects gene expression. In sum, there is a physical mark of the outer rim of the wing and other epithelia in Drosophila.
• Prof. Sonja-Verena Albers, University of Freiburg: New players in FtsZ-based cell division in Archaea Speaker Series. The event is co-hosted by the Microbiology Seminar Series, Max Planck Institute for Terrestrial Microbiology, Marburg, and as such can also be attended online. After the lecture and the public discussion, there will be a Meet & Greet of MiNu's doctoral researchers with Prof. Albers.
• Prof. Martin Thanbichler: Role of NTPases in the spatiotemporal organization of bacterial cells PI Lecture
• Prof. Michal Hocek, Charles University, Prague (CZ): Base-modified nucleotides and nucleic acids for chemical biology, medicinal chemistry and diagnostics Speaker Series. The Hocek group is interested in synthetic, bioorganic and medicinal chemistry of nucleic acids and their components. Novel types of modified derivatives and analogues of nucleobases, nucleosides, nucleotides and nucleic acids are designed and prepared for applications in all areas of biomedicinal sciences (medicinal chemistry, biochemistry, chemical biology, bioanalysis etc.). Basic developments of methodology for the synthesis of these modified biomolecules are performed largely using modern methods (including metal- or enzyme-catalyzed reactions). Biological activity (antitumor, antiviral etc.) of the novel nucleobases, nucleosides and nucleotides is systematically studied in collaboration with several groups both in academia and in pharmaceutical industry, including mechanism of action and preclinical development of promising new cytostatics. Enzymatic synthesis of functionalized nucleic acids bearing diverse interesting and useful substituents is developed and the modified oligonucleotides or nucleic acids are applied in bioanalysis (redox labelling for electrochemical detection or environment-sensitive fluorescence labelling for fluorescent microscopy) or in chemical biology (regulation of gene expression or cross-linking of DNA probes with proteins).
• Dr. Maria Duca, Université Côte d’Azur, Nice (FR): Design of multifunctional conjugates for the targeting of non-coding RNAs: anticancer and antimicrobial applications Speaker Series. Abstract: RNA is one of the most intriguing and promising biological targets for the discovery of innovative drugs in a large number of pathologies and various biologically relevant RNAs that could serve as drug targets have already been identified. Among the most important ones, it is worth to mention prokaryotic ribosomal RNA which is the target of a number of currently employed antibiotics, viral RNAs such as TAR, RRE and DIS RNA of HIV-1 or oncogenic microRNAs that are tightly involved in the development and progression of various cancers. However, difficulties in the rational design of strong and specific small-molecule ligands renders this kind of molecules relatively rare. In this presentation, we will show our recent results about the structure-based design of new RNA ligands targeting oncogenic RNAs that led us to the identification of new compounds bearing a promising biological activity but also to a better understanding of the formed interactions toward the design of optimized compounds. In parallel to the design of bioactive compounds, we also perform the screening of chemical library thus increasing the available chemical tools for the development of efficient and specific RNA binders for a wide number of therapeutic applications. We will finally show the validation of a new antibacterial target and the design of original compounds bearing potential antimicrobial activity against resistant bacterial strains.
• Prof. Lars-Oliver Essen: Theoretical and experimental analysis of structural dynamics PI Lecture
• Dr. Marcus Lechner: 6S RNA - Universal Regulator of Transcription PI Lecture
• Prof. Lennart Randau: CRISPR-based regulation of bacterial gene networks PI Lecture
• Dr. Murat Sunbul, Heidelberg University: Illuminating biology with fluorescent RNAs Speaker Series. After the lecture, MiNu's doctoral researchers will have the opportunity for discussions with Dr. Sunbul.
• 2024 Summer Symposium Invited speakers: Prof. Iwona Mruk (University of Gdansk), Prof. Ben Luisi (University of Cambridge), Dr. Georg Hochberg (MPI Marburg), Dr. Rebecca Hinrichs (University of Marburg), Prof. Kristina Jonas (Stockholm University), Prof. Urs Jenal (University of Basel).
• 2024 Retreat Annual closed meeting of MiNu's doctoral students, PIs and selected external researchers
• Dr. Maximilian Ulbrich, University of Freiburg: Single-molecule imaging of membrane protein interactions in living cells Speaker Series. Background information: the Ulbrich Lab is part of the BIOSS Centre for Biological Signalling Studies and the  Faculty of Medicine at the University of Freiburg, and a member of the Spemann Graduate School of Biology and Medicine. Research in the Ulbrich Lab lab focusses on interactions of membrane proteins in living cells, trying to understand how complexes made of many different proteins assemble and how they behave during signalling processes. To this purpose, single fluorescent molecules are imaged using state-of-the art microscopy equipment and develop novel tools for single molecule imaging. Current projects include the dynamic behaviour of G protein-coupled receptors, the assembly of glutamate receptors with their auxiliary subunits, and super-resolution imaging.
• Workshop Week Symposium With talks by Dr. Benedict Tan (Pharmaceutical Chemistry, University of Marburg), Prof. Kai Thormann (Microbiology, University of Gießen), Dr. Patricia Bedrunka (SYNMIKRO, PI of GRK 2937's Project 9, University of Marburg) and Prof. Haike Antelmann (Microbiology, University of Berlin).
• Prof. Anthony Poole, University of Auckland (NZ): Experimental evolution sheds insights on the intracellular lifestyle Speaker Series. Abstract: Intracellularity leads to some quite unusual changes to genomes and to nucleotide metabolism. I will present the results of two studies that make use of experimental evolution for to examine the evolution of two phenomena. In the first project, I will present work from our lab on the impact of knocking out genes for ribonucleotide reduction in the bacterium E. coli. We document the dependence of these bacteria on externally-supplied deoxyribonucleosides, mimicking the loss of this process in some intracellular bacterial species, including Ureaplasma, Borrelia and Buchnera. Our experiment revealed subsequent gene losses that were also found to have naturally occurred in these species. The paradox we observed was that the gene losses that emerged following loss of ribonucleotide reduction prevented the potential for evolution to make use of an alternative mechanism for dNTP synthesis, suggesting that a short term benefit trumps the long term potential in this system. The second project involves the serial bottlenecking of E. coli to see whether genetic drift hastens the emergence of genomic errors that can be corrected via slippage (during) or via editing (after) transcription. Such processes are quite common in intracellular bacteria such as Buchnera, but also are found in eukaryotic organelles of bacterial origin. Our results show that, under conditions favouring genetic drift, we do indeed observe an increased probability of the evolution of these processes. We conclude that our experiments support the idea of constructive neutral evolution, a process by which genetic drift leads to more complex molecular processes with no immediate advantage. In both cases, the ancestral state did not require the capacity for slippage or editing, but, at the end of the experiment, loss of such processes would unmask sublethal mutations - the genomes must now be corrected during gene expression to avoid this.
• Prof. Mario Mörl, Leipzig University: Synthetic Riboswitches: From Plug & Pray towards Plug & Play Speaker Series. Detailed information coming soon.
• Prof. Malcolm White, University of St Andrews (SCO): Cyclic nucleotide signalling in antiviral defence Speaker Series. The research interests of the White Lab centre around the discovery and molecular understanding of bacterial anti-viral defence systems using a combination of molecular biology, microbiology, biochemistry, bioinformatics and structural biology. New enzymes for molecular biology and the repurposing CRISPR systems for new diagnostic assays is the industrial relevance of the Lab's work.
• Prof. Jue Wang, University of Wisconsin-Madison and Mercator Fellow of GRK 2937: Themes and Variations of Stress-Signaling Alarmones Speaker Series. About the Wang Lab: Bacterial stress responses allow cells to survive fluctuating environments, antibiotic treatments, and host defenses. My current research aims to answer the following fundamental questions: how do bacteria utilize stress-induced small molecules to adapt to their specific environmental niches? How do bacteria enter a metabolically dormant persister state that is intrinsically tolerant to a broad array of antibiotic treatments? How do stressed bacteria mitigate potential conflicts between their DNA replication and transcription machineries to ensure survival? What are the molecular mechanisms of bacterial evolution to fit their specific niches? We combine metabolomics, transcriptomics, and proteomics with biochemical and evolutionary approaches to answer these questions. We study these processes in the Gram-positive bacterium Bacillus subtilis and the Gram-negative bacterium Escherichia coli. These organisms grow fast and are highly amenable to genetic manipulation. Because the fundamentals of information processing mechanisms are conserved across all domains of life, our work in bacteria is broadly applicable to other, less tractable, systems.
• Dr. Olivier Duss, European Molecular Biology Laboratory (EMBL) Heidelberg Speaker Series. More information coming soon.
• Prof. Birte Höcker, University of Bayreuth Speaker Series. More information coming soon.
• Prof. Patrick Viollier, Université de Genève: Specificity of sialate cytidyltransferases in flagellin glycosylation and polymerization Speaker Series. More information coming soon.