This project investigates the role of the JAK signalling pathway in the antiviral immune response against the varicella-zoster virus (VZV). The focus is on how JAK-dependent mechanisms influence VZV lytic infection and spread among epithelial, T, and nerve cells. Through genetic and pharmacological modifications of JAK signalling, the project aims to characterise cell-type-specific antiviral responses and identify host factors that are relevant to viral replication and spread. Additionally, primary cells from individuals with altered JAK signalling will be analysed. The results will contribute to a better understanding of the increased susceptibility to VZV infection during JAK inhibitor therapy and to elucidate key JAK-dependent antiviral protective mechanisms.
This project investigates how the varicella-zoster virus (VZV) influences the innate immune response during productive infection and reactivation from neuronal latency. The focus is on the viral proteins pVLT63 and IE63, which modulate key interferon-mediated antiviral mechanisms. In particular, the study examines the cellular proteins and RNAs with which both viral proteins interact, as well as possible functional differences between the viral proteins. Using epithelial cells and iPSC-derived sensory neurons, the project aims to identify relevant antiviral host factors and characterize their role in controlling VZV infection and reactivation. The project aims to elucidate fundamental mechanisms of viral immune evasion and contribute to a better understanding of how VZV can overcome the interferon response and enable successful infection or reactivation.
The project investigates how cells recognise long, aberrant nuclear RNAs (lanRNAs) that arise during an HSV-1 infection or as a result of cellular stress responses. The focus is on the hypothesis that these RNAs act as cellular danger signals and, particularly after activation by interferons, can trigger programs such as cell death. The study examines the RNA sensors and signalling pathways involved, as well as the mechanisms by which lanRNAs are normally degraded. In addition, the project aims to clarify why different cell types react with varying sensitivity to their accumulation. Using various infection and disease models, the functional significance of this mechanism in controlling HSV-1 and other stress conditions is being investigated. The project aims to elucidate a novel connection between RNA quality control, cellular stress response, and antiviral immunity
The project investigates how host RNA-binding proteins influence infection with influenza A virus (IAV) and contribute to the antiviral interferon (IFN) response. The focus is on IFN-stimulated genes encoding proteins that bind directly to viral RNA and thereby limit viral replication. Based on previously identified candidates, their mechanisms of action and effects on viral RNA functions will be characterized. In addition, the study will investigate how RNA-binding proteins orchestrate the IFN response to IAV infection on a global level. Functional analysis of selected host factors will be conducted in human lung epithelial cells and in more complex respiratory tract models. The project aims to uncover new RNA-directed regulatory mechanisms of innate antiviral immunity and to identify previously unknown cellular restriction factors.
This project investigates how genetic variation in both the host and pathogen shapes the immune response to Pseudomonas aeruginosa infection, with a particular focus on the regulation of interferon responses in severe infection. By combining diverse clinical P. aeruginosa strains with human macrophage models and integrating single-cell and multi-omics data, the project aims to define the molecular determinants of variation in host immune responses. Through integrative computational analysis of genetic, transcriptomic, and epigenetic information, the study will establish a comprehensive framework for understanding host–pathogen interactions and identify key regulatory networks and signalling pathways underlying disease severity. Ultimately, the project aims to uncover mechanisms that could inform the development of new therapeutic strategies for P. aeruginosa infections.
The project investigates how autophagy and mitochondrial functions jointly contribute to the defense against intracellular infections with Salmonella Typhimurium. The focus is on the protein IRGQ, which plays an important role in the targeted removal of cellular and possibly also bacterial components. The study investigates how the activation of the kinase TBK1 regulates the function of IRGQ and its interaction with autophagy proteins. Furthermore, the research aims to clarify how IRGQ influences mitochondria during an infection and thereby modulates immune responses. The underlying mechanisms are being characterized using molecular, cell biological, and animal models. The goal is to better understand the connection between pathogen elimination, mitochondrial homeostasis, and inflammatory responses, and to uncover key mechanisms of cellular defense against infection.
This project investigates how changes in mitochondrial function influence the defence against intracellular infections with Listeria monocytogenes in intestinal epithelial cells. The focus is on the interplay between mitochondrial dynamics, cellular immune responses, and PGC-1α, the key regulator of mitochondrial biogenesis. Preliminary studies show that Listeria specifically interferes with these processes and can thereby promote bacterial proliferation, whereas interferon signalling enhances mitochondrial function and antibacterial defence. Using cell lines, intestinal organoids, and mouse models, the underlying mechanisms and pathogen-specific differences will be investigated. The goal is to identify key metabolic and signalling pathways that link mitochondrial homeostasis and immune defence, and to determine whether specifically modulating these pathways can improve the control of bacterial infections.
This project investigates the roles of type I and type III interferons (IFNs) in orchestrating the intestinal epithelial immune response to Salmonella enterica. Specifically, it aims to delineate the cell-type-specific responses to each IFN and elucidate how their downstream signaling pathways modulate key outcomes, including intracellular bacterial replication, epithelial barrier integrity, and mucosal inflammation. This work aims to identify IFN-stimulated genes and associated epigenetic modifications induced during infection. Additionally, the project explores the crosstalk between enteric neurons and the intestinal epithelium, assessing how this neuro-immune interaction shapes IFN-mediated antibacterial defense. Using a combination of intestinal organoids, neuronal co-culture systems, and multi-omics approaches we will dissect the underlying molecular mechanisms. Ultimately, this research seeks to provide a comprehensive understanding of the cell-type-specific IFN responses and their functional significance in controlling intestinal bacterial infections.