All Projects

Funding: MWK, 2.903.582 EUR

Project Details:
Development and testing of preventive and therapeutic measures against SARS-CoV-2 using experimental animal models such as ferrets, rabbits, hamsters and primates.

Funding: MWK, 11.851.000 EUR

Project Details:
Carrying out an animal experiment to test monoclonal antibodies in the established hamster model at the RIZ, including applying for animal experiments, carrying out the animal experiment, virus titration and analyzes to determine the viral load in the organs, PCR analysis, histopathological examination (assay scope of 2 organs per animal).

Funding: Deutsches Zentrum für Luft- und Raumfahrt e.V. (DLR), DLR-Projektträger (BMBF, Zoonosenplattform), 237.000 EUR

Project Details:
Allein in Deutschland erkranken pro Jahr über eine halbe Million Menschen an einer Lungenentzündung.
Auch in der Schweinehaltung führen Atemwegsinfektionen zu einer Krankheitslast und hohen
wirtschaftlichen Verlusten. Dabei stellt die Entstehung von resistenten Erregern neue Herausforderungen
an die Human- und Veterinärmedizin. Zur Entwicklung neuer Behandlungsstrategien ist das Verständnis
der Wirt-Erreger-Interaktionen in komplexen Ko-Infektionsmodellen elementar.
Influenza-A-Virus (IAV) Infektionen und bakterielle Ko-Infektionen sind als eine Kombination für schwere
Krankheitsverläufe bei Mensch und Schwein beschrieben. Die bakteriellen Erreger sind oftmals
Kommensale des oberen Atemtraktes und der Tonsillen. Häufig sind die Auslöser für bakterielle
Lungeninfektionen mit schwerem akutem Verlauf unklar. In unseren Vorarbeiten haben wir
interessanterweise für einige humane und porcine bakterielle Lungenerreger einen unerwarteten Phänotyp
im Zusammenhang mit DNA-Netzen ("neutrophil extracellular traps, NETs") identifiziert. Dieser spezielle
Abwehrmechanismus von Neutrophilen wird aus extrazellulären DNA-Strukturen der Neutrophilen gebildet
und ist ursprünglich als eine antimikrobielle Strategie gegen Infektionserreger beschrieben. Unsere Daten
zeigen, dass NETs einigen bakteriellen Erregern als Lieferant für Wachstumsfaktoren wie z.B. NAD dienen
und somit eine Vermehrung von NAD-abhängigen Bakterien im Wirt verbessern. Damit wird die Aussage
der antimikrobiellen Wirkung von NETs für einige Erreger in Frage gestellt. Dieser Phänotyp wird stärker,
wenn DNasen vorhanden sind, die das Grundgerüst der NETs verdauen und somit den NETs Abbau im
Wirt regulieren. Da IAV NETs induzieren können, soll die Wirt-Erreger Interaktion bei Ko-Infektionen von
IAV und bakteriellen Erregern in Mensch und Schwein mit dem Fokus auf die Rolle der NETs untersucht
werden. Die Kernfrage ist, inwiefern IAV-induzierte NETs-Bildung die Ausbreitung von bakteriellen Ko-
Infektionen triggert.

Cooperation Partners:

Prof. Dr. Barbara Kahl (Universitätsklinikum Münster (UKM), Institut für Medizinische Mikrobiologie)

Prof. Dr. Matthias Mörgelin (Colzyx AB, Lund, Schweden)

Project Details:
Several studies, including those of our research groups, have shown that certain inflammatory mediators including neutrophil extracellular traps (NETs) and DNase activity may be of relevance during and after stroke. Therefore, we analyse human cohorts to identify new insights in this research topic.

Results:

Grosse GM, Blume N, Abu-Fares O, Götz F, Ernst J, Leotescu A, Gabriel MM, van Gemmeren T, Worthmann H, Lichtinghagen R, Imker R, Falk CS, Weissenborn K, Schuppner R, de Buhr N. 2022. Endogenous Deoxyribonuclease Activity and Cell-Free Deoxyribonucleic Acid in Acute Ischemic Stroke: A Cohort Study. Stroke 53.

Cooperation Partners:

Cerebrovascular Research Group (Head: Prof. Dr. Karin Weissenborn), Dept. of Neurology, MHH: Dr. Ramona Schuppner & Dr. Gerrit M. Grosse, Dr. Maria Gabriel, PD Dr. Hans Worthmann

Funding: DFG, 335.000 EUR

Project Details:
The equine recurrent uveitis (ERU) is the most important eye disease in horses, but the exact pathogenesis is still not fully understood. Furthermore, the recurrent uveitis is also found in human as well as almost all domesticated animals. Since autoreactive antibodies are detectedable in diseased horses, the classical ERU is considered as an autoimmune disease. The classical form of ERU is characterized by an acute serofibrinous and plasmacellular inflammation of the ciliary body, iris, choroidea and other eye structures. The disease often results into a chronic form by recurring intervallic relapses. The impulses lead to a progressive destruction of intraocular structures and finally lead to blindness.
Besides autoimmune processes, Leptospira infections are discussed to contribute to ERU in humans, horses, dogs and cattle. In over 60% of ERU-diseased horses Leptospira interrogans has been detected in the VBF using PCR or microscopic agglutination test (MAT). Additionally, the microbiological culture of Leptospira interrogans from VBF has been proven in further studies. Nevertheless, the role of the pathogen in the pathogenesis of ERU is still controversially discussed. Since the eye is protected via special barriers as one of the immune-privileged compartments in the body, the immigration of protective immune cells into the eye is highly regulated. A damage of the blood retina barrier is a typical pathological feature of ERU and often leads to a large number of migrating immune cells into the eye. The question arises whether the barrier is disrupted by infectious agents such as Leptospira, or whether the infection is a consequence of the immune-mediated pathogenesis of the ERU. These questions have not been fully clarified yet. However, irrespective of the Leptospira detection in ERU-diseased horses, the pathogenesis of ERU seems to be a highly complex altered immune reaction of the eye. Interestingly, in some populations an accumulation of different leukocyte populations as granulocytes can also be found in ERU patients, which have been histologically detected in the retina. However, especially the role of neutrophil granulocytes in ERU is still unclear and the focus of this project.

Results:

Neutrophil Extracellular Traps in the Pathogenesis of Equine Recurrent Uveitis (ERU).

Fingerhut L, Ohnesorge B, von Borstel M, Schumski A, Strutzberg-Minder K, Mörgelin M, Deeg CA, Haagsman HP, Beineke A, von Köckritz-Blickwede M, de Buhr N.

Cells. 2019 Nov 27;8(12). pii: E1528. doi: 10.3390/cells8121528.

 

Fingerhut L, Dolz G, de Buhr N. 2020. What Is the Evolutionary Fingerprint in Neutrophil Granulocytes? Int J Mol Sci 21:1-37.

 

Fingerhut L, Yücel L, Struzberg-Minder K, von Köckritz-Blickwede M, Ohnesorge B, de Buhr N. 2022. Ex Vivo and In Vitro Analysis Identify a Detrimental Impact of Neutrophil Extracellular Traps on Eye Structures in Equine Recurrent Uveitis. Front Immunol 13:1-20.

Cooperation Partners:

Prof. Dr. Cornelia Deeg, Philipps Universität Marburg, FB Medizin, Experimentelle Ophthalmologie, Marburg

Prof. Dr. Andreas Beineke, Institute for Pathology, TiHo

Dr. Katrin Strutzberg-Minder, IVD, Hannover, Germany

Prof. Dr. Henk Haagsman, Department of Infectious Diseases & Immunology, Division Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Netherlands

Funding: DFG, 265.456 EUR

Project Details:
Charakterisierung ausgewählter Viren, die in Wildreservoirs identifiziert wurden, Bewertung ihres Risikos für Haustiere und Menschen.

Funding: DFG, 256.546 EUR

Project Details:
Identifizierung und Charakterisierung neuartiger Vogel-Metapneumoviren von Wildvögeln, die eine Bedrohung für Hausgeflügel und Säugetiere darstellen.

Funding: DFG, 329.905 EUR

Project Details:
The VIPER research and training program will cover the global chain of events involved in virus emergence, all the way from virus discovery, isolation, molecular characterization, surveillance, and pathogenesis, towards animal and public health impact and intervention strategies including new approaches for prevention and control.

The VIPER research projects are subdivided into three pillars:

virus discovery, host range and transmission
virus-host cell interactions and pathogenesis, and
immune interference and intervention strategies.

Funding: DFG, 329.905 EUR

Project Details:
The VIPER research and training program will cover the global chain of events involved in virus emergence, all the way from virus discovery, isolation, molecular characterization, surveillance, and pathogenesis, towards animal and public health impact and intervention strategies including new approaches for prevention and control.

The VIPER research projects are subdivided into three pillars:

virus discovery, host range and transmission
virus-host cell interactions and pathogenesis, and
immune interference and intervention strategies.

Results:

1) https://pubmed.ncbi.nlm.nih.gov/35491822/

(Geiselhardt F, Peters M, Jo WK, Schadenhofer A, Puff C, Baumgärtner W, Kydyrmanov A, Kuiken T, Piewbang C, Techangamsuwan S, Osterhaus ADME, Beineke A, Ludlow M. Development and Validation of a Pan-Genotypic Real-Time Quantitative Reverse Transcription-PCR Assay To Detect Canine Distemper Virus and Phocine Distemper Virus in Domestic Animals and Wildlife. J Clin Microbiol. 2022 May 18;60(5):e0250521. doi: 10.1128/jcm.02505-21. Epub 2022 May 2. PMID: 35491822; PMCID: PMC9116185.)

 

2) https://pubmed.ncbi.nlm.nih.gov/36038706/

(Geiselhardt F, Peters M, Kleinschmidt S, Chludzinski E, Stoff M, Ludlow M, Beineke A. Neuropathologic and molecular aspects of a canine distemper epizootic in red foxes in Germany. Sci Rep. 2022 Aug 29;12(1):14691. doi: 10.1038/s41598-022-19023-9. PMID: 36038706; PMCID: PMC9424316.)

Funding: EU, 295.313 EUR

Project Details:
Untersuchung von Mechanismen und Modellen, die die Zugänglichkeit von Therapeutika (IM2PACT) für das Gehirn vorhersagen