All Projects

Funding: DFG, 498.400 EUR

Project Details:
The equine recurrent uveitis (ERU) is the main reason for blindness in horses, and 10% of the european horses are affected. Significantly, ERU is an important available model for human autoimmune uveitis as the clinical and immune-pathological characteristics are similar. As a cause for ERU, various hypotheses are described in the literature. On the one hand, infections with Leptospira interrogans are discussed as well as other bacterial, parasitic or viral infections. Independent of the initiating cause, there are numerous indications that ERU is an immune-mediated disease. In the body after the control of the primary infection, an overreaction of the immune system occurs in response to activated immune cells. In addition to lymphocytes, these immune cells can also be neutrophil granulocytes. Among various antimicrobial functions, neutrophils have been shown to release neutrophil extracellular traps (NETs). NETs are extracellular DNA fibers with associated proteases and antimicrobial peptides which are released by activated cells. NETs mediate entrap of invading pathogens, but when massively released may contribute to detrimental autoimmune reactions of the host.
The research project presented here is intended to provide essential insights for the involvement of NETs in the pathogenesis of ERU. In the first phase of our study, our findings indicate an involvement of NETs in the pathogenesis of ERU with detrimental effects. In short, NETs correlate to disease severity, seem to damage the blood retinal cells, and induce autoantibodies against NET proteins. We hypothesize, that those autoantibodies might shield the NETs from degradation by DNases, resulting in their persistence and potentially in new disease episodes. Thus, in the current project we aim to characterize if and how the phase of disease (non-active quiescent phase versus acute inflammatory phase) influences cellular involvement and extracellular DNA release. Based on our previous data, we further hypothesize that different cell types besides neutrophils play a role in extracellular DNA release during the progression of ERU, which enables crosstalk between various immune cells. Therefore, we will study the release of ETs by other immune cells besides neutrophils and its interplay with adaptive immune cells. Finally, since the use of gentamicin in the treatment of ERU patients is well established, the aim is to determine the influence of gentamicin in varying concentrations and along with distinct stimuli on equine immune cells, focusing on ET release.
 

Funding: Niedersächsisches Ministerium für Wissenschaft und Kultur (MWK), 324.000 EUR

Project Details:
The aim of this subproject is the further development and optimization of a 3D lung epithelial cell culture model
for the investigation of viral and bacterial infections and the effect of immunomodulatory
immunomodulatory substances on the course of infection and cell biochemical processes. An increased
complexity of the model system using physiological or pathophysiological oxygen
conditions and microfluidic systems enables the in vitro system to be approximated to the in vivo situation and
to the in vivo situation and will help to reduce the number of test animals in the long term. The
complexity of the infection model is reduced by physiologically relevant oxygen conditions (defined
tissue-specific hypoxic conditions) and by 3D co-cultivation of human or animal pulmonary
or animal pulmonary epithelial cells and neutrophil granulocytes. In addition
the use of primary cells and induced pluripotent stem cells should provide long-term optimization.

Funding: MWK, 540.878 EUR

Project Details:
Comprehensive characterization of the hormone profiles of the HPG axis in male and female Long COVID patients, hormone panels, hormone measurements and statistical evaluations.
Creation of expression profiles of sex hormones and
sex hormone receptors in the plasma, lungs, reproductive organs and brains of male and female hamsters.

Results:

https://www.umg.eu/forschung/corona/cofoni/

Project Details:
-

Cooperation Partners:

Zentrum für systemische Neurowissenschaften (ZSN), Hannover

Institut für Neuroimmunologie und Multiple-Sklerose-Forschung (IMSF) der Universitätsmedizin Göttingen, Göttingen

Funding: Roland und Elfriede Schauer-Stiftung, 210.000 EUR

Project Details:
In this project, we hypothesize that glycosylated C-type lectin receptor (CLR) ligands induce a differential expression of CLRs by intestinal macrophages under bacterial dysbiosis, thereby leading to a modulated host immune response. This hypothesis will be tested by performing in vitro and in vivo studies.

Funding: MWK, 104.704 EUR

Project Details:
COFONI LZF-TP-Expansion to include the research area
"Interdisciplinary research into the long-term consequences of SARS-CoV-2 pandemic

Results:

https://www.umg.eu/forschung/corona/cofoni/

Funding: MWK via UMG (COFONI), 86.260 EUR

Project Details:
Type I interferon signaling and mitochondrial dysfunction in the heart acute and long-Covid disease.

Results:

https://www.umg.eu/forschung/corona/cofoni/

Funding: MWK, 104.704 EUR

Project Details:
COFONI-LPC TechnologiePlattform 2-
Animal models & test systems

Results:

https://www.umg.eu/forschung/corona/cofoni/

Funding: DFG (VIPER GRK)

Project Details:
The exact pathomechanisms that lead to the development of long-term consequences after an acute SARS-CoV-2 infection - also known as long-COVID - are still largely unknown. Since only limited sample material from surviving patients with long-COVID is available, the use of a suitable animal model is essential to investigate the underlying mechanisms. In this project, the Syrian golden hamster was established as a model animal to study the pathogenesis of long-COVID. Initially, a short-term study was conducted to investigate the alveolar regeneration mechanisms, in which a morphological homology to the processes in the human lung after s SARS-CoV-2 infection was found. In a further long-term study over four months, morphological, molecular biological and lung function analyses were combined. The course of the disease in the animals showed three phases: acute, subacute and chronic. While the acute phase was characterized by severe breathing restrictions, these only occurred after exercise in the later phases and disappeared entirely after about 6 weeks. Histologically, there was persistent fibrosis and alveolar bronchiolization with club cell proliferation. Transcriptome analysis showed, among other things, an upregulation of pro-fibrotic genes. In the future, long-term consequences in the brain will be investigated primarily by transcriptome analysis, and the role of the pulmonary neuroendocrine system, which is connected to the central nervous system via afferent nerve fibers, will be examined in more detail.

Results:

Paper 1: https://www.nature.com/articles/s41467-023-39049-5 ; Nature Communications, 2023

 

Paper 2: https://www.researchsquare.com/article/rs-4681343/v1 ; (preprint Version), accepted at Nature Communications, 2025

Funding: DFG (VIPER GRK)

Project Details:
The aim of the project was to identify mechanisms of immune interference of canine distemper virus (CDV) in cells of innate immunity, in particular with regard to the antagonization of the innate antiviral immune response. For this purpose, different primary cell cultures were created from canine isolated immune cells and infected with different strains of CDV. The focus of the work was on alveolar macrophages, as these cells play a crucial role as primary target cells of the virus after aerogenic CDV infection and are furthermore essential for the maintenance of alveolar homeostasis. Differences in the response of immune cells to CDV infection were investigated using immunofluorescence staining, RT-qPCR, virus titration, RNA sequencing and assays to quantify cell death and viability.

Results:

https://pubmed.ncbi.nlm.nih.gov/39796262/

Cooperation Partners:

Helmholtz-Zentrum für Infektionsforschung, Genomanalytik (Robert Geffers)