Annual Conference 2025 of the Association for General and Applied Microbiology - Jahrestagung 2025 der Vereinigung für Allgemeine und Angewandte Mikrobiologie

Prof. Dr.

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Prof

The role of genetic and environmental factors in driving gene regulatory rewiring patterns

FG Regulation

How does novelty arise in evolution? Is the process solely based on chance or might we be able to discern rules for the evolution of innovation? Are there genetic or environmental factors that might predispose particular adaptive routes over others to the evolution of novelty? Work from my lab addresses these questions using a combination of molecular genetic manipulations and experimental evolution, within the context of gene regulatory networks, using a bacterial model system. We have shown that pre-existing gene regulatory network structures bias repurposing of certain transcription factors by facilitating promiscuity. And that, transcription factor activity (and by extension the environment) has the potential to drive adaptive potential for regulatory rewiring and innovation. These insights advance our understanding of the evolutionary accessibility of particular transcription factors for innovation, with broad implications for understanding and predicting bacterial adaptation to novel environments.

Invited lecture

Placing and counting – spatial regulation of flagellation in bacteria

Many bacteria possess flagella, helical proteinaceous rotating filaments, which enable active motility in various environments. The flagellar apparatus is an intricate nanomachine, which is synthesized from a range of different building blocks of various stoichiometries. A complex regulation pattern underlies the stepwise formation of flagellar subunits, resulting in an inside-out assembly of the flagellar apparatus.Notably, flagellation occurs in species-specific pattern. In many environments, the monopolar flagellation (a single flagellum at one cell pole) is the predominant pattern. In these cells, flagellar synthesis has to be targeted to the appropriate cell pole, and, additionally, the number of flagella has to be restricted to a single one. For many bacterial species, this flagellation pattern is governed by the SRP-type GTPase FlhF as the polarity factor and the MinD-like ATPase FlhG as the flagella counting factor. In recent studies, we developed a model describing how onset of flagella synthesis is spatially controlled and how flagella formation is shut down to restrict the number of flagella to a single one. This model along with the implications and many still open questions will be presented here.

Short lecture

Two tales of transcriptional regulator evolution

Bacteria need to adapt constantly to changing environmental conditions such as temperature, pH or nutrient availability. In addition, they may encounter toxic compounds, which are either produced by co-habitants or used in industrial or clinical setting to eliminate bacterial contaminations and infections. Transcriptional regulators, which can either repress or activate the expression of their cognate regulon, play an important role for these adaptation processes in bacteria. The human pathogen Listeria monocytogenes is ubiquitously found in nature and can easily adapt to changing environmental conditions. It can also easily enter food-processing facilities, which results in the production of contaminated food products. Disinfectants that usually contain quaternary ammonium compounds are used to eliminate bacterial contaminations in food-processing facilities. We could show that L. monocytogenes can easily become tolerant to these compounds by loss-of-function mutations in transcriptional repressors, which regulate the expression of efflux systems. Upon ingestion of contaminated food products, L. monocytogenes can switch to a pathogenic lifestyle and cause mild or severe infections depending on the immune status of the patient. This switch is dependent on the activity of the main virulence regulator PrfA, which controls the expression of most virulence genes of L. monocytogenes. Virulence gene expression is a costly process for the bacterium, thus expression and activity of PrfA needs to be tightly regulated and adapted in response to environmental factors. Regulation of PrfA takes place on transcriptional, posttranscriptional and posttranslational level to ensure that PrfA is only active, when L. monocytogenes enters its host. However, under certain conditions, L. monocytogenes can acquire gain-of-function mutations in PrfA leading to an enhanced virulence gene expression independent of the environmental conditions. All together, bacteria can easily adapt to changes in the environment by alterations in the gene expression due to mutations in regulatory systems.

Investigating signaling network evolution phenomena in the fungus Magnaporthe oryzae

Research in evolutionary dynamics has demonstrated that – apart from bacteria – also eukaryotic organisms like fungi can undergo rapid evolutionary changes within a "very short" timeframe. The molecular mechanisms driving these rapid adaptations remain poorly understood, largely due to their dependence on rare and unpredictable changes. Adaptive evolution in microorganisms typically involves advantageous genetic, transcriptomic, or proteomic changes that persist through natural selection. Understanding these mechanisms is crucial for addressing global challenges such as the emergence of new pathogens, the spread of invasive species, and the development of multi-drug resistance.Within this work the rice blast pathogen Magnaporthe oryzae is used to highlight the complexity of evolution in regulatory networks of physiological and biochemical processes. The High Osmolarity Glycerol (HOG) pathway regulates cellular adaptation to environmental osmolarity. Loss-of-function (lof) mutants of the HOG pathway are osmosensitive and fail to produce the main critical osmotic stress response solute arabitol as it is in the wildtype strain. Interestingly, when these lof mutants are exposed to constant osmotic pressure, stable suppressor strains emerge that produce high amounts of the osmolyte glycerol instead of arabitol.This study aimed to identify the genes responsible for adaptation to long-term stress and the shift from arabitol to glycerol production. Candidate genes were identified and their roles in primary metabolite production. Within this work an effective bioinformatic pipeline for label-free quantification of proteome and phosphoproteome data was developed. Using M. oryzae as a model, a data-independent acquisition (DIA) approach was developed, significantly improving the quality and completeness of the data. This method reduced the LC-MS/MS analysis time and increased the identification of phosphosites, establishing a refined methodology and a comprehensive basis for studying signaling processes in filamentous fungi. Within this method, a new set of candidate genes involved in the adaptation process was identified. These findings contribute to a deeper understanding of the complex evolutionary mechanisms in M. oryzae and underscore the need for continued research to unravel the molecular basis of rapid evolutionary adaptations in microorganisms.

FG Regulation
Evolution of regulation

Appointment

Chair

Programme

FG RegulationEvolution of regulation

Appointment

Chair

Programme

FG Regulation
Evolution of regulation