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 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 Jens Hör investigates the dynamics of infection, host takeover, and anti-phage defense during the interaction between RNA phages and their hosts. They seek to understand the molecular principles underlying these processes to develop new and improved antibacterial strategies such as phage therapy.

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.

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 Julian König works on deciphering how RNA processing is controlled by RNA binding proteins and RNA modifications. By integrating transcriptomic, biochemical, and functional genomics approaches, the group seeks to decode the RNA regulatory code. Their ultimate goal is to translate insights from fundamental research into an understanding of human physiology and disease.

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 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.

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 Zarnack group focuses on understanding the molecular mechanisms of RNA regulation in human cells and how their dysregulation contributes to disease. Using transcriptomic data and advanced bioinformatics, we explore the intricate interplay of RNA-binding proteins, RNA modifications and additional factors in nuclear and cytoplasmic processes, including alternative splicing, 3' end processing, nuclear surveillance, and RNA decay.

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.

The Beusch group studies regulatory mechanisms which steer the assembly of the spliceosome but also allow it to handle its very diverse substrate pool. We tackle this problem with an interdisciplinary approach by combining genetics & genomics with molecular biology & biochemistry. By gaining a detailed mechanistic understanding of splicing and its regulation within the cell, we can not only understand fundamental eukaryotic biology but also how its dysregulation impacts human disease.

The Papadopoulos group focuses on understanding the molecular mechanisms that maintain aggressive human cancers. We are particularly interested in the MYC oncoprotein family and how their newly discovered RNA-binding functions mitigate DNA damage and prevent immune recognition in rapidly proliferating cancer cells.

The goal of the Petri group is to deploy novel RNA-guided gene editing technology to enhance immune cell therapies. To do this, we a) develop new RNA-guided editing tools, b) evaluate their safety using state-of-the-art molecular methods, and c) apply them to enhance immune cell therapies. With a particular focus on oncologic diseases, we aim to streamline the application and safety-validation of RNA-guided gene editing tools to generate and enhance immune cell products for cancer patients.