Würzburg RNA Ecosystem

The research group led by Jörg Vogel investigates the RNA world of microbes during infection and in the context of their natural habitat. Using high-resolution methods, they seek to understand when, how and why bacteria use RNA-based mechanisms to regulate their genes, and exploit this knowledge to develop RNA-based therapeutic approaches.

The research group led by Chase Beisel works at the interface of CRISPR biology and technologies. They investigate the functional diversity of CRISPR-Cas immune systems to develop new technologies that can be employed to better understand, diagnose and treat human infections.

The research group led by Lars Barquist works on the development of new statistical, bioinformatic, and visualization approaches to functional genomics data. They bring together sequencing data and new computational technologies to provide new insights into bacterial pathogenesis and advance RNA-based therapeutics.

The research group lead by Neva Caliskan investigates functions and dynamics of RNA molecules in noncanonical translation events, which can affect the interplay between the host and pathogen during infection. Ultimately, they seek to illuminate therapeutic RNA-protein complexes as novel targets to combat infections.

The research group led by Mathias Munschauer investigates host and pathogen RNA-protein interactions in an infection context. They work towards obtaining a mechanistic understanding of RNA functions during infection, which will ultimately aid the development of host-directed therapeutics.

The research group led by Emmanuel Saliba explores host-pathogen interactions in high resolution at the single-cell level. They develop and integrate single-cell genomics, imaging and computational approaches to decipher the microenvironments of individual pathogens and shed light on the heterogeneity of host responses and disease outcomes.

The research group led by Redmond Smyth investigates how RNA viruses use RNA structure during their replication and evolution. They seek to exploit knowledge of RNA genomic architecture to advance the development of targeted RNA-based therapeutics.

The research group led by Alexander Westermann investigates molecular RNA-based mechanisms underlying the interplay between the host, invading pathogens and the host microbiota. They seek to identify potential molecules and metabolic pathways to target in diagnostics and therapeutics.

The research group led by Franziska Faber investigates the interplay between the enteric pathogen Clostridioides difficile and the intestinal microbiota. They seek to better understand the RNA-based mechanisms controlling virulence during these interactions. The goal is to leverage this knowledge for the development of novel RNA-based antimicrobials.

Herpesviruses are large DNA viruses, which co-evolved with their human and animal hosts for millions of years. The Dölken lab employs a systems biology approach to study host cell modulation and immune evasion in various herpesviruses. The researchers pioneered metabolic labelling of newly transcribed RNA using 4-thiouridine (4sU)-tagging to analyze short-term changes in RNA synthesis, processing and decay at both population (4sU-seq) and single-cell level (Record-seq). Also, they study RNA synthesis, processing, export, translation and stability in lytic herpes simplex virus 1 infection in order to understand the coordinated regulation of gene expression by viral proteins, microRNAs and RNA-binding proteins and their functional relevance in infection. Comparative analyses are performed using the murine and human cytomegalovirus model.

The Fischer group studies the functional dynamics of macromolecular machines acting on RNA using a combination of biochemical, structural and systems biology approaches. By combining basic RNA research with biomedical approaches, the scientists also investigate how RNA-based pathways and networks are changed in different disease settings and in viral infections.

Cell fate decision is essential for the emergence of a complex multicellular organism starting from a single pluripotent zygote, and perpetually occurs during adult life to maintain organ tissues. The robustness of cell fate decision is remarkable given the stochastic interaction of hundreds of thousands of molecules in each cell. It has remained a central open question how signals from the microenvironment are integrated with stochastic processes in a cell to control cell fate decision in normal tissues and upon perturbations due to disease or tissue damage. The Grün lab investigates these questions in the context of immune cell differentiation by combining single-cell RNA-seq methods with computational approaches involving machine learning and mathematical modeling.

• Chemical biology of natural RNA/DNA modifications
• Nucleic acid chemistry
• DNA catalysis
• Ribozymes and aptamers
• Biomolecular label chemistry
• Structure and mechanism of functional nucleic acids and RNA protein complexes

The research group led by Katharina Markmann seeks to understand the molecular mechanisms underlying systemic control of plant root endosymbioses with bacteria and fungi, and the role of regulatory small RNAs therein. They further analyze the role of systemically mobile small RNAs in controlling plant developmental responses to biotic and abiotic stimuli.

Biological interfaces:

• Bioresponsive systems (diagnostics and therapy)
• Pharmaceutical functionalization of biomaterials
• Formulation of proteins, chemical drugs and therapeutic gases

Chemical-physical interfaces:

• Transformation of drugs into ionic liquids

The Rudel lab studies molecular mechanisms how the major human pathogenic bacteria Chlamydia trachomatis, Neisseria gonorrhoeae and Staphylococcus aureus cause diseases. The group’s research focuses on the interaction of these pathogens with different host cells and how this disturbs the normal function of the cell and the innate immune and cell autonomous defense. One particular aspect in this context is the role of bacterial (sRNAs) and human regulatory RNAs (microRNAs) during the infection process. The researchers aim to understand invasive (S. aureus sepsis; disseminating gonococcal infection) and chronic diseases (Chlamydia ovarian cancer connection) by employing new infection models on the basis of engineered human three dimensional tissues.

The Sendtner lab focuses on mechanisms of subcellular distribution of RNA and control of RNA translation, protein synthesis in axonal branch points and axon terminals of motor neurons. RNA binding proteins such as TDP-43 and FUS play important roles in the binding and processing of RNA and protein complexes in the nucleus as well as the cell body of motor neurons. In their research projects, the scientists have observed in motor neurons the effects of mutations in the genes for SMN, TDP-43, and FUS. This leads to distribution defects of mRNA molecules, which include the RNAs for various actin isoforms. Changes in translational control for protein synthesis of these proteins in axon terminals and their branch points were also observed. These changes result in the inability of nerve impulses to be transmitted to muscles. Among the important goals of the group’s research is to improve or restore this impaired function in axonal nerve cell processes.

The Sharma lab focuses on how bacterial pathogens adapt to changing environments and control their virulence. They aim to unravel mechanisms and functions of gene regulation via small RNAs (sRNAs) and associated RNA binding proteins (RBPs) as well as small proteins. Their main model organisms are the gastric pathogen Helicobacter pylori and the related foodborne pathogen Campylobacter jejuni. They have been developing and employing diverse deep-sequencing approaches (e.g. RNA-seq, Ribo-seq, RIP-seq) for global transcriptome and translatome analysis and to study RNA-protein complexes.

Using genomics, genetics, and biochemical approaches, they aim to identify and characterize RNA and protein factors, such as RBPs and ribonucleases, involved in post-transcriptional regulation in bacterial pathogens. Using three-dimensional (3D) infection models based on tissue engineering, they are investigating the roles of sRNAs, small proteins, and RBPs in virulence of H. pylori and C. jejuni. Moreover, they are exploring mechanisms and functions of bacterial CRISPR-Cas immune systems, leading to new biotechnological applications.

In ageing Western societies tumors are becoming the most relevant medical problem. Key characteristics of tumors are deregulated signaling pathways that significantly alter the transcriptional profile of tumor cells. Proteins of the MYC family play a prominent role in this oncogenic reprogramming as transcription factors. The vision of the Wolf group is to understand the transcriptional changes during carcinogenesis and, in particular, the oncogenic function of MYC to the extent that new pharmaceutical strategies for the fight against cancer can be developed on this basis. To this end, the Wolf lab uses genome- and proteome-wide methods to better understand the biology of tumors as well as genetic screens to find potential therapeutic targets of tumor cells. Together with their partners, the researchers have recently developed substances that inhibit the function of MYC. In the next few years, the Wolf group wants to improve these molecules of the PROTAC substance class to such an extent that they can be clinically tested and applied.

Urinary tract infections (UTIs) caused by Gram-negative uropathogenic Escherichia coli (UPEC) are among the most common and recurrent infections worldwide. Up to now, most of the anti-infective research has been focused on combating the bacterial side. However, whether a person is susceptible to infection by UPEC is also decided by host factors. Hence, host-based therapeutics represent an innovative approach to fight infections. The Aguilar group aims to obtain a better understanding of the host pathways controlling UPEC infection and persistence in the bladder. The researchers use adult stem cell derived-organoids and organoid-based models to closely mimic the natural infection site. They combine these infection models with miRNome profiling (global analysis of host microRNA expression), single-cell RNA-sequencing, and gain/loss-of-function approaches in order to identify and functionally characterize specific host factors and/or pathways that are required for UPEC to infect and persist in the human bladder epithelium. Based on this knowledge, new host-based therapeutic approaches could be designed to prevent or treat UTIs.

The Backes group is interested in studying RNA-based mechanisms in virulence, virus replication and host defense.