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Würzburg RNA Ecosystem

The Würzburg RNA Ecosystem is characterized by interdisciplinary research and technology centers such as the Biocenter and the Single-Cell Center. The Helmholtz Institute for RNA-based Infection Research (HIRI) closely cooperates with various partners such as the Max Planck and Fraunhofer Societies to foster local interdisciplinary research.

Würzburg RNA Ecosystem: Institutions

Institute for Molecular Infection Biology

The Institute for Molecular Infection Biology (IMIB) at the Julius-Maximilians-Universität of Würzburg (JMU) is an interdisciplinary research institution of the Medical Faculty with strong links to the Faculty of Biology. Jörg Vogel, who is also director of the HIRI, has been director of the institute since 2009.

The internationally recruited scientists at IMIB investigate the molecular mechanisms of infections caused by bacteria, parasites and fungi. They aim to elucidate fundamental aspects of gene regulation of pathogens and to identify common strategies employed by the pathogens when interacting with host cells and the immune system.

Another focus of the institute lies in the analysis of small RNAs and other non-coding RNA molecules in infection. This is complemented by a research technology infrastructure that aims at developing new applications for sequencing-based approaches like single-cell RNA-seq, multi-organism-RNA-seq and
tissue RNA-seq.

Single-Cell Center Würzburg

In 2021, the HIRI co-founded the Single-Cell Center Würzburg to further advance one of its core technologies. The Center is a joint venture with the Faculty of Medicine of JMU, the University Hospital Würzburg (UKW), the Fraunhofer Translational Center for Regenerative Therapies (TLZ-RT), and the Max Planck Research Group at the Würzburg Institute of Systems Immunology (WüSI).

The center’s objective is to analyze and understand diseases at the level of individual cells. In the future, this will enable the earliest possible and most reliable prediction of a disease and how it can be treated in the best possible way. The center combines local scientific, clinical and methodological expertise relevant to innovative single-cell research and provides access to the full range of scRNA-seq technologies for both eukaryotes and microorganisms.

Starting from infection research, the Würzburg Single-Cell Center will also investigate cancer, neurodegenerative disorders or cardiovascular diseases at the single cell level. The broad method spectrum of RNA sequencing technologies is to be rapidly enhanced in this context.

Detect a disease before it emerges? This is how single-cell research may help:

Core Unit SysMed

The Core Unit Systems Medicine (SysMed) is a joint institution of the JMU Medical Faculty and the University Hospital. It works closely with the HIRI and other research institutes. It provides scientists with the technology and bioinformatics support for RNA and DNA sequencing for biomedical research. A particular focus of the unit is the application of single-cell RNA sequencing. The establishment of additional subunits for the support of large-scale data analyses and modelling are in progress.

Biocenter

The Biocenter is an amalgamation of departments and chairs from the Faculties of Biology, Medicine and Chemistry, collaborating in research and teaching. It unites scientists who share the conviction that the great questions of biology and medicine can only be answered if they are tackled on each of the organizational levels of biology − from molecules, cells, organs and the whole organism, to interactions between organisms.

Consequently, researchers at the Biocenter are developing the latest methods in molecular biology, cell biology and organismic biology and applying them closely to their respective scientific research.

Research is being done using almost all important model organisms of the animal and plant kingdoms, including Arabidopsis, Drosophila, honey bees, the mouse, xenopus, yeast and zebrafish. Technologies at the interface of several disciplines − such as advanced microscopy, High Through­put Screening, DNA sequencing and metabolome analysis − are organized as central facilities.

Medical Faculty (JMU)

The Medical Faculty of the Julius-Maximilians-Universität of Würzburg (JMU) has a strong connection to the University Hospital, founded on scientific research carried out in close cooperation with clinical institutes.

By transcending traditional clinical research areas and exchanging them for three novel complexity-oriented research foci the faculty aims to represent itself in its entirety more effectively, to overcome borders between traditional disciplines, and to foster interdisciplinarity. The three newly defined research foci are: (I) cellular heterogeneity, (II) complexity within organ tissues and (III) system and network diseases. Focusing on these research foci does not dispense from the necessity of excellent discipline-specific research; they rather provide a cross-disciplinary framework for joint projects that may eventuate in collaborative research initiatives. 

Research within the Medical Faculty is structurally supported by platform technologies such as micros­copy, mass spectrometry, transgene technologies, and systems medicine.

University Hospital Würzburg

The University Hospital Würzburg (UKW) is devoted to medical care, research and teaching, which facilitates progressive counselling and treatment of patients according to the highest current standards in medical care: First-class medicine and research that benefits all patients.

The hospital assumes a central role in providing high quality medical care to the people of Würzburg and the surrounding region. It consists of 19 clinics and three autonomous policlinics as well as four clinical institutes. Each year, UKW takes care of about 74,000 stationary patients, plus more than 270,000 out­patient treatments.

In addition, the hospital is involved in several clinical research centers, where interdisciplinary cooperation takes the center stage: Amongst others these are the Comprehensive Cancer Center Mainfranken, the Interdisciplinary Center for Palliative Medicine and the Comprehensive Heart Failure Center.

UKW is an important resource for many scientists providing them with tissue samples for basic research again highlighting the local scientific network and support structures.

RNA Faculty Members

Jörg Vogel

RNA Biology of Bacterial Infections

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.

Chase Beisel

RNA Synthetic Biology

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.

Lars Barquist

Integrative Informatics for Infection Biology

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.

Neva Caliskan

Recoding Mechanisms in Infections

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.

Mathias Munschauer

Long Non-coding RNA and Infection Biology

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.

Emmanuel Saliba

Single-Cell Analysis

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.

Redmond Smyth

Genome Architecture and Evolution of RNA Viruses

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.

Alexander Westermann

Host-Pathogen-Microbiota Interactions

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.

Franziska Faber

RNA Biology of Gram-positive Bacteria

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.

Lars Dölken

RNA Biology in Viral Infections

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.

Florian Erhard

Systems Virology

The Erhard lab develops new computational and statistical approaches to make use of data from high-throughput experiments and, by using those, studies host cell modulation and immune evasion in various herpesvirus models. Among others, the researchers have developed new bioinformatics methods to identify miRNA targets (PARCLIP), for quantitative analysis of next-generation sequencing, for finding translated short ORFs (Ribo-seq) and to precisely distinguish newly transcribed and pre-existing RNA (SLAM-seq). They apply these tools to study systems biology of herpesviruses including fundamental properties of microRNA targeting, the role of viral and cellular sORFs in virus-host interaction and immune evasion and the kinetic behavior of gene regulation during infection.

Utz Fischer

RNA Metabolism and Macromolecular Machines

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.

Dominik Grün

Quantitative Single-Cell Biology of the Immune System

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.

Claudia Höbartner

Organic and Biomolecular Chemistry

  • 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

Lorenz Meinel

Drug Formulation and Delivery

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

Thomas Rudel

Bacteria-Host Interaction

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.

Michael Sendtner

Clinical Neurobiology

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.

Cynthia Sharma

Deep Sequencing Approaches to Pathogenesis

The Sharma lab focuses on mechanisms and functions of small RNAs (sRNAs) and RNA binding proteins (RBPs) in the gastric pathogen Helicobacter pylori and the food-borne pathogen Campylobacter jejuni. The researchers have been 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 protein factors involved in post-transcriptional regulation. Moreover, the Sharma group is interested in RNA localization in prokaryotes and has been studying the Type II CRISPRCas9 nuclease in C. jejuni. Using 3D infection models based on tissue engineering, the researchers investigate the role of sRNAs and RBPs in virulence.

Elmar Wolf

Cancer Systems Biology

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.

Carmen Aguilar

Host Pathways in Urinary Tract Infections

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.

Simone Backes

Roles of RNAs During Virus Infection

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

More about RNA research in Würzburg

The research foci of the Helmholtz Institute