Research Foci
Rising antimicrobial resistance, chronic infections, and (re-)emerging pathogens are among the major challenges facing humanity. As a federal institute, the Helmholtz Institute for RNA-based Infection Research (HIRI) pioneers an integrative approach to exploit the vast potential of RNA as a diagnostic, drug, and therapeutic target for new strategies to combat infectious diseases.
Three central research areas
Led by Director Jörg Vogel, the HIRI focuses on three central areas: Basic research on bacterial pathogens, on viruses and on the host response by the immune system. These three fields are complemented by applied research on diagnostics and RNA delivery for therapeutic purposes. The integration of emerging topics in RNA research, such as RNA modifications, will ensure a place for the HIRI at the forefront of infectious disease research. Core technologies, with a major focus on sequencing approaches, are harnessed for high-throughput exploration of RNA functions and will provide an opportunity to construct a systems-level view of the role of ribonucleic acids (RNA) during infection.
The mRNA vaccine against COVID-19 very clearly demonstrates how therapeutic agents based on ribonucleic acids can be developed and customized very quickly. We want to take advantage of this adaptability in order to develop new tailor-made therapeutics to combat infectious diseases.
Jörg Vogel (Read more in this interview)
Integrated scientific concept
With its integrated scientific concept and cutting-edge infrastructure, the HIRI provides a vibrant research environment for both established and young scientists. The natural synergy between this new institute and the infection research and translational competences at the University of Würzburg as well as at the Helmholtz Centre for Infection Research (HZI) Braunschweig creates unique opportunities to effectively convert knowledge into applications. This setting also stimulates collaborations with industry in the development of novel therapeutic and diagnostic strategies for the treatment of infectious diseases.
Bacterial Infections
Despite improved prevention and treatment options, bacterial pathogens remain a major cause of life-threatening acute and chronic disease worldwide. The prevalence of multidrug resistant bacteria in hospitals now threatens the considerable advances of modern medicine. Moreover, infections as well as the intake of broad-spectrum antibiotics can cause dramatic changes in the microbiota, with ramifications for the development and manifestation of seemingly unrelated diseases.
In the field of bacterial infections the HIRI aims to develop new ways to rapidly diagnose and treat bacterial infections. A major goal is the comprehensive simultaneous RNA-based profiling of the pathogen and the infected host in real time and at high resolution; where applicable, this should also include co-colonizing microbiota. The scientists in this area then focus on the mode of action of RNA molecules that are crucial for the synthesis of virulence traits of the pathogen, differentially expressed upon exposure to the host, or that impact gene expression in interacting members of the microbiota. This knowledge is then exploited for therapeutic intervention with clinically relevant bacterial pathogens.
Viral infections
Viruses are responsible for millions of acute and chronic infections, partly associated with devastating consequences such as lifelong disability, cancer or death. Many of these infections lack effective vaccines or treatments. Moreover, the majority of emerging infections likely to cause global epidemics are of viral origin. Therefore, research on viral pathogenesis, the identification of novel drug targets, and drug development are of major public interest.
With regard to viral infections, HIRI scientists aim to unravel the role of RNA in productive viral infections and persistence. This includes understanding viral noncoding RNAs (ncRNAs) and regulatory elements, as well as host cellular RNA targeted by the virus. Scientists in this area are establishing new in-vitro and in-vivo models for the development and pre-clinical evaluation of a new generation of antivirals interfering with ncRNA functions.
Host response
The host response to infections involves complex interactions between pathogens, host cells, and the host immune system. During an infection, cells of the innate and adaptive immune system undertake a coordinated effort to control the pathogen, requiring major changes in the expression of both coding and noncoding transcripts. These RNA expression changes are shaped by both the pathogen and the activation of intrinsic host defence mechanisms, including the secretion of chemo- and cytokines. Control of these mechanisms is needed to prevent either pathogen survival or immunopathology, and crucially depends on intricate RNA-based regulatory networks.
Scientists in this area aim to dissect the complex intercellular and subcellular RNA networks involved in the control of infection. Key goals are the comprehensive RNA-based profiling of cell type-specific responses during infection and the identification of novel RNA markers and mechanisms. HIRI investigates the functions of ncRNAs and RNA elements regulated by and regulating the host response to bacterial and viral infections. The knowledge obtained is utilised for therapeutic interventions, with the goal of modulating the host response to infection and limiting pathogenesis.
RNA Delivery
The spread of antimicrobial resistance and emergence of new pathogens drive the need to expand the anti-infective arsenal. In this regard, RNA-based therapeutics and RNA-binding drugs such as RNA silencers, therapeutic ribozymes and aptamers, RNA-based genome editing tools and tailor-made mRNAs provide exciting opportunities for intervention in pathogen activity and for host protection.
Basic research at the HIRI is complemented by applied research on RNA delivery, which in turn will develop delivery technologies acting in concert with chemically optimized RNA drugs to treat infectious diseases. This requires interdisciplinary research at the interface of clinical medicine, life sciences, (nano-) material sciences and pharmaceutical research. Analytical studies are essential for successful translation, including thermodynamic, mechanic, and structural characterization of complex RNA delivery systems. In addition, process analytical techniques (PAT), quality-by-design approaches and stringent stability studies require implementation during manufacture, as do validated analytical methods, importantly high-performance liquid chromatography. Advanced physico-chemical analytics generated by this field are fundamental to the translation of nucleotide/RNA drug research into the clinics.
Bacterial Infections
Despite improved prevention and treatment options, bacterial pathogens remain a major cause of life-threatening acute and chronic disease worldwide. The prevalence of multidrug resistant bacteria in hospitals now threatens the considerable advances of modern medicine. Moreover, infections as well as the intake of broad-spectrum antibiotics can cause dramatic changes in the microbiota, with ramifications for the development and manifestation of seemingly unrelated diseases.
In the field of bacterial infections the HIRI aims to develop new ways to rapidly diagnose and treat bacterial infections. A major goal is the comprehensive simultaneous RNA-based profiling of the pathogen and the infected host in real time and at high resolution; where applicable, this should also include co-colonizing microbiota. The scientists in this area then focus on the mode of action of RNA molecules that are crucial for the synthesis of virulence traits of the pathogen, differentially expressed upon exposure to the host, or that impact gene expression in interacting members of the microbiota. This knowledge is then exploited for therapeutic intervention with clinically relevant bacterial pathogens.
Viral infections
Viruses are responsible for millions of acute and chronic infections, partly associated with devastating consequences such as lifelong disability, cancer or death. Many of these infections lack effective vaccines or treatments. Moreover, the majority of emerging infections likely to cause global epidemics are of viral origin. Therefore, research on viral pathogenesis, the identification of novel drug targets, and drug development are of major public interest.
With regard to viral infections, HIRI scientists aim to unravel the role of RNA in productive viral infections and persistence. This includes understanding viral noncoding RNAs (ncRNAs) and regulatory elements, as well as host cellular RNA targeted by the virus. Scientists in this area are establishing new in-vitro and in-vivo models for the development and pre-clinical evaluation of a new generation of antivirals interfering with ncRNA functions.
Host response
The host response to infections involves complex interactions between pathogens, host cells, and the host immune system. During an infection, cells of the innate and adaptive immune system undertake a coordinated effort to control the pathogen, requiring major changes in the expression of both coding and noncoding transcripts. These RNA expression changes are shaped by both the pathogen and the activation of intrinsic host defence mechanisms, including the secretion of chemo- and cytokines. Control of these mechanisms is needed to prevent either pathogen survival or immunopathology, and crucially depends on intricate RNA-based regulatory networks.
Scientists in this area aim to dissect the complex intercellular and subcellular RNA networks involved in the control of infection. Key goals are the comprehensive RNA-based profiling of cell type-specific responses during infection and the identification of novel RNA markers and mechanisms. HIRI investigates the functions of ncRNAs and RNA elements regulated by and regulating the host response to bacterial and viral infections. The knowledge obtained is utilised for therapeutic interventions, with the goal of modulating the host response to infection and limiting pathogenesis.
RNA Delivery
The spread of antimicrobial resistance and emergence of new pathogens drive the need to expand the anti-infective arsenal. In this regard, RNA-based therapeutics and RNA-binding drugs such as RNA silencers, therapeutic ribozymes and aptamers, RNA-based genome editing tools and tailor-made mRNAs provide exciting opportunities for intervention in pathogen activity and for host protection.
Basic research at the HIRI is complemented by applied research on RNA delivery, which in turn will develop delivery technologies acting in concert with chemically optimized RNA drugs to treat infectious diseases. This requires interdisciplinary research at the interface of clinical medicine, life sciences, (nano-) material sciences and pharmaceutical research. Analytical studies are essential for successful translation, including thermodynamic, mechanic, and structural characterization of complex RNA delivery systems. In addition, process analytical techniques (PAT), quality-by-design approaches and stringent stability studies require implementation during manufacture, as do validated analytical methods, importantly high-performance liquid chromatography. Advanced physico-chemical analytics generated by this field are fundamental to the translation of nucleotide/RNA drug research into the clinics.