Focus of Research

Infections with seasonal influenza A and B viruses, commonly known as “the flu” can cause severe lung disease when the human innate immune response fails to control virus replication. Research of the Brunotte Lab focuses on the vibrant battle between virus and host. Using state of the art and novel methodology, we investigate the molecular weapons employed by respiratory RNA viruses to exploit and reprogram intracellular resources to enforce viral replication and the opposing multifaceted, complex antiviral defense mechanisms of the host. To this end, we dive deep into the processes of viral genome replication and host immunology.

For our research we apply and develop primary infection models of the human upper and lower respiratory tract to study organ-specific innate immune responses within the native and multicellular tissue environment. We specifically focus our work on the virus host interactions at the respiratory epithelium and the alveolar immune cell compartment using single cell technology in order to unravel the mechanisms that contribute to the development of critical immune responses and also affect the replication of viral and bacterial pathogens.

In addition to human adapted viruses, we are also interested in the molecular biology of zoonotic and highly pathogenic influenza viruses that circulate in wild birds and pose an increasing pandemic risk to humans. Here, we elucidate the viral mechanisms of immune activation that often lead to overshooting and uncontrollable cytokine responses, known as “cytokine storm” and cause sever multiorgan damage. Using reverse genetics and direct RNA sequencing, we aim to unravel viral or host factors that qualify as novel drug targets for antiviral or immune-modulatory treatments.

Finally, within the framework for pandemic preparedness, we develop new methods and employ our established primary respiratory tract infection models to enhance our understanding on the pathogenicity mechanisms and to improve the experimental toolbox for the risk assessment of highly pathogenic avian influenza viruses.

We are open for applications for highly motivated bachelor and master students who are interested to study RNA viruses and the induced immune responses! Please send your written application and motivation letter via email to linda.brunotte@uni-giessen.de.

Prof. Dr. rer. nat. Linda Brunotte
Prof. Dr. rer. nat. Linda Brunotte

Lab Members

Post Docs

Dr. rer. nat. Saskia Sophie Hinse
Dr. rer. nat. Saskia Sophie Hinse
Project description: My research focuses on understanding how different lung cell types respond to infection, with a particular interest in viral infections and their impact on lung health and disease. I mainly work with human lung models, including tissue explants, organoid systems, and isolated cell types such as alveolar type 2 (AT-2) cells and macrophages. These models allow me to study cellular responses in a controlled setting.
My current projects include (1) studying bacterial co-infection during viral pneumonia, focusing on the role of outer membrane vesicles (OMVs); (2) characterizing AT-2 derived lung organoids to explore regeneration, differentiation, and infection responses; and (3) analysing alveolar cell composition and structural remodeling in COPD.
Dr. rer. nat. Sriram Kumar
Dr. rer. nat. Sriram Kumar
Project description: My research aims to understand the cell-intrinsic molecular mechanisms and cell type-specific immune responses driving respiratory virus infections, with the goal of developing novel host-directed therapies. To achieve this, I employ advanced multiomic approaches and mechanistic functional assays in clinically relevant human lung models to resolve antiviral and inflammatory signatures at single-cell resolution. My current projects include (1) Characterizing the distinct immune-repertoire and therapeutic potential of interferon-α subtypes against influenza and coronaviruses, (2) Evaluating interferon-based combination therapies with approved antivirals to improve efficacy and prevent emergence of drug resistance, and (3) Pharmacological inhibition of the transcriptional master regulator TRIM28 as a therapeutic strategy for infection-induced hyperinflammation.

PhD Students

Lioba Franziska Böhm, M.Sc.
Lioba Franziska Böhm, M.Sc.
Project description: Driven by the recent emergence of avian influenza A viruses (IAV) of the clade 2.3.4.4b, this project aims to define the immunopathological signatures of novel zoonotic strains. Given that highly pathogenic avian influenza viruses (HPAIV) can differ in their immune activation relative to human-adapted IAV, we will investigate the phosphorylation patterns of immune-regulatory kinases, particularly in the TRIM28 cascade, and pro-inflammatory cytokine profiles of uncharacterised strains. To further elucidate the mechanisms of virulence, we will analyse the immune regulatory function of the viral non-structural protein 1 (NS1) as well as mutation-specific effects on host immune response.
Jana Mareike Brand, M.Sc.
Jana Mareike Brand, M.Sc.
Project description: My research focuses on the molecular mechanisms that determine the pathogenicity of Influenza A viruses (IAVs), with a particular interest in highly pathogenic avian influenza viruses (HPAIVs). I investigate how deletion-containing viral genomes (DVGs) and mini viral RNAs (mvRNAs) shape host immune responses and contribute to disease severity. The projects I am working on aim to characterize strain-specific DVG signatures, unravel the mechanisms of DVG biogenesis and RNA structural determinants, and define their role in innate immune activation. Ultimately, my research seeks to establish DVGs as novel biomarkers for pandemic risk assessment and to explore their potential as antiviral and immunomodulatory therapeutic tools.