Research

Funding: Deutsche Forschungsgemeinschaft (DFG), 155.950 EUR

Project Details:
Abstract:
Canine distemper virus (CDV) is a highly contagious morbillivirus, which causes severe systemic disease with involvement of the respiratory tract in domestic and wildlife carnivores. Innate immune cells play a key role in the pathogenesis in a variety of viral respiratory diseases. However, the knowledge about pulmonary innate immunity in canine distemper is still fragmentary. The envisioned project is based on our previous work, in which it could be demonstrated that innate immune cells are able to carry CDV to facilitate cell-to-cell transmission in the respiratory tract and that restriction of antiviral signaling pathways of innate immune cells enhance virus release from the lung in canine distemper. The first part of the project aims at investigating the polarizing effect of CDV upon innate immune cells in vitro. Here the ability of CDV to influence the phenotype of pulmonary and blood-derived macrophages, and the maturation state of monocyte-derived dendritic cells will be analyzed by flow cytometry. In addition, virus-mediated effects upon macrophages and dendritic cells will be characterized by whole transcriptome analyses and functional assays, including mixed leukocyte reaction, as well as migration, phagocytosis and nitric oxide release assays. In the second part, the impact of macrophage polarity and dendritic cell maturation upon CDV cell entry and the capacity of modulated innate immune cells to transmit CDV to the airway epithelium will be investigated using canine air-liquid interface cultures and precision-cut lung slices. In addition, virus-induced cytopathic effects and ultrastructural changes, such as ciliary pathology and apoptosis induction, as well as the regenerative capacity of infected cultures will be determined. The study will give mechanistic insights in the dysfunction of pulmonary innate immunity in CDV infection and its impact on disease pathogenesis. Elucidating the regulatory mechanisms through which pathogens regulate innate immune cell plasticity will contribute to the discovery of therapeutic targets in morbillivirus diseases and prevention of virus transmission to other hosts.

Funding: Deutsche Forschungsgemeinschaft (DFG), 155.950 EUR

Project Details:
Abstract:
Canine distemper virus (CDV) is a highly contagious morbillivirus, which causes severe systemic disease with involvement of the respiratory tract in domestic and wildlife carnivores. Innate immune cells play a key role in the pathogenesis in a variety of viral respiratory diseases. However, the knowledge about pulmonary innate immunity in canine distemper is still fragmentary. The envisioned project is based on our previous work, in which it could be demonstrated that innate immune cells are able to carry CDV to facilitate cell-to-cell transmission in the respiratory tract and that restriction of antiviral signaling pathways of innate immune cells enhance virus release from the lung in canine distemper. The first part of the project aims at investigating the polarizing effect of CDV upon innate immune cells in vitro. Here the ability of CDV to influence the phenotype of pulmonary and blood-derived macrophages, and the maturation state of monocyte-derived dendritic cells will be analyzed by flow cytometry. In addition, virus-mediated effects upon macrophages and dendritic cells will be characterized by whole transcriptome analyses and functional assays, including mixed leukocyte reaction, as well as migration, phagocytosis and nitric oxide release assays. In the second part, the impact of macrophage polarity and dendritic cell maturation upon CDV cell entry and the capacity of modulated innate immune cells to transmit CDV to the airway epithelium will be investigated using canine air-liquid interface cultures and precision-cut lung slices. In addition, virus-induced cytopathic effects and ultrastructural changes, such as ciliary pathology and apoptosis induction, as well as the regenerative capacity of infected cultures will be determined. The study will give mechanistic insights in the dysfunction of pulmonary innate immunity in CDV infection and its impact on disease pathogenesis. Elucidating the regulatory mechanisms through which pathogens regulate innate immune cell plasticity will contribute to the discovery of therapeutic targets in morbillivirus diseases and prevention of virus transmission to other hosts.

Funding: Landesbetrieb für Küstenschutz, Nationalpark und Meeresschutz Schleswig-Holstein, 49.580 EUR

Project Details:
The ITAW has been conducting research on marine mammals for more than 30 years and, with over 50 employees at the institute in Büsum, has sufficient highly qualified professionels on hand. The aim of the scientists is to investigate the ecology and physiology of marine mammals and to assess the impacts of humans on the animals, their health and their population.
In the project "Monitoring of marine mammal strandings", all reporting forms completed by the seal hunters are digitized and transferred to a database. This reporting forms are filled in by the seal hunters of Schleswig-Holstein for every stranded marine mammal, both for stranded sick or dead animals, and contain information on stranding date, location, species and condition of the animal/carcass. This data is summarized and evaluated annually in order to investigate trends in stranding numbers for the three resident marine mammal species and to assess the possible causes for the stranding. Furthermore, the data is regularly cross-referenced with the data from the cases investigated at the ITAW. This enables a more comprehensive and objective assessment of the situation of the native marine mammal population. In addition, more complex scientific evaluations can be carried out than before and the resulting findings can be used directly by the responsible authorities for the further development of existing management plans.

Funding: DFG, 482.000 EUR

Project Details:
Streptococcus suis is a frequent colonizer of the upper respiratory tract of pigs, but can also cause severe systemic diseases like meningitis and septicemia. However, pathogenesis of S. suis infection and the role of its virulence-associated factors, namely the pore-forming toxin suilysin (SLY) and the D-alanine-D-alanyl carrier ligase (DltA), is still not fully understood. So far, it is known that SLY damages different host cells by lytic pore formation and induces an inflammatory response leading to the release of cytokines, especially by monocytes/macrophages, and the recruitment of neutrophils. D-alanylation of lipoteichoic acids in the cell wall by DltA is known to increase resistance against antimicrobial peptides (AMPs) and phagocytosis of S. suis by neutrophils.
Our aim is to clarify the role of SLY and DltA in S. suis colonization of the porcine respiratory tract, systemic dissemination via the bloodstream, and invasion of the central nervous system. Thereby we will focus on their influence on innate immunity cells and the crosstalk between monocytes/macrophages and neutrophils. We hypothesize that the host compartments influence the expression of sly and dltA differentially and that vice versa SLY and DltA influence the host’s innate immune response by modulating the crosstalk between neutrophils and monocytes/macrophages contributing to the resistance of. S. suis towards immune defense mechanisms.
To investigate this, we will use complex in vitro cell culture systems that closely mimic the in vivo situation of the three main host compartments: a co-culture system of primary respiratory epithelial cells differentiated under air-liquid interface conditions and alveolar macrophages, porcine precision-cut lung slices, a reconstituted whole blood model, and the blood cerebrospinal fluid barrier model. Infection experiments will be performed with S. suis serotype 2 wild-type strain (wt), its isogenic mutants Δsly, ΔdltA, and ΔdltAΔsly as well as the respective complemented mutant strains.
We will start with the analysis of sly and dltA expression in the three compartments by quantitative real-time PCR and Western blotting, followed by the investigation of the neutrophil and the monocyte/macrophage response towards S. suis wt and sly- and dltA-deficient mutants. We will focus on the formation of neutrophil extracellular traps, reactive oxygen species production, phagocytic activity, and the release of certain cytokines and AMPs. Finally, we will investigate how secretions from monocytes/macrophages induced by S. suis infection influence neutrophils regarding their transmigration, inflammatory response, and phagocytic capacity, and vice versa.
The detailed investigation of the innate immune response towards S. suis infection in the three different compartments will help to better understand the switch of S. suis as a colonizer to an invasive pathogen, and how SLY and DltA are involved in this process.

Cooperation Partners:

Dr. Sophie Öhlmann (Institut für Bakteriologie und Mykologie, Veterinärmedizinische Fakultät, Universität Leipzig)

Funding: Pfizer, 246.000 EUR

Project Details:
Tick-borne diseases are a major health concern, with Lyme disease and early summer meningoencephalitis (TBE) among the most important. Although it is known that ticks infected with Borrelia in particular are almost ubiquitous, there is no comprehensive, area-wide picture of tick infection rates and thus the human risk of infection. Using a sample set of thousands of ticks, a reliable picture of Borrelia prevalence in Germany will be obtained for the first time.
The data on tick infections obtained, together with the data on tick density from the previous project, will enable the identification of factors associated with high local Borrelia prevalence.
In addition, tick pools from selected locations, e.g. TBE endemic areas or those where human TBE cases have occurred in the respective county, will be examined for TBE virus infections.

Results:

Topp, A.-K., Springer, A., Mischke, R., Rieder, J., Feige, K., Ganter, M., Nagel-Kohl, U., Nordhoff, M., Boelke, M., Becker, S., Pachnicke, S., Schunack, B., Dobler, G., Strube, C. (2023) Seroprevalence of tick-borne encephalitis virus in wild and domestic animals in northern Germany. Ticks and Tick-Borne Diseases 14, 102220

Cooperation Partners:

Prof. Dr. G. Dobler, Nationales Konsiliarlabor für FSME, München

Dr. V. Fingerle, Nationales Referenzzentrum für Borrelien, Oberschleißheim

Dr. O. Kahl, tick-radar GmbH

Prof. Dr. U. Mackenstedt, Universität Hohenheim

Prof. Dr. M. Pfeffer, Universität Leipzig

Funding: Deutsche Forschungsgemeinschaft (DFG) , 404.650 EUR

Project Details:
The genus Pestivirus belongs to the virus family Flaviviridae and comprises RNA viruses of great relevance, like Bovine viral diarrhea virus (BVDV) and Classical swine fever virus (CSFV), which are causative pathogens of notifiable diseases. Since decades, it was commonly accepted that pestivirus infections are restricted to cloven hooved (ungulate) hosts. In the past years, several atypical pestiviruses have been discovered in non-ungulate hosts. These newly discovered pestiviruses show the typical genome organization, but are genetically highly distinct. Obviously, these novel viruses represent a new group within the pestiviruses with so far uncharacterized biological properties. In addition, such a novel pestivirus was also discovered in pigs and designated "atypical porcine pestivirus" (APPV). APPV causes a neurological disease in newborn piglets (congenital tremor) and involvement in other diseases (e.g. infertility, abortion, neonatal malformations) appears likely.
Within this research project, it was possible to adapt APPV to cell culture conditions and to propagate it. The availability of a virus isolate provided the basis for further studies to characterize the biological properties of the pathogen. Our work demonstrated that there are obviously significant differences in the cell entry of APPV and CSFV. It has been believed for long time that the complement-regulating protein CD46 is the key for pestiviruses to penetrate the host cell, but our work showed that some pestiviruses - including CSFV - use a CD46-independent mechanism for cell entry. Which cellular surface structures are used instead for cell entry is still unclear and will be the subject of further research.
The aim of the study is to provide insights into the complex, probably multi-step process of cell entry. Within this project is the aim to identify the molecular determinants of cell entry of pestiviruses and to characterize them in more detail. Several host cell factors have already been identified which apparently interact with the viral envelope proteins during early phases of viral replication and can influence virus replication. First, it has to be elucidated whether these factors directly interact with the virus particles or whether these are indirect effects, e.g. caused by binding to other cellular proteins or by an altered cell metabolism. Knowledge of the key factors for the entry of porcine pestiviruses into the host cell can make a valuable contribution to understanding the biology of the new and widespread pathogen in the pig population, APPV, as well as the properties of the long-known animal disease pathogen CSFV.

Results:

https://www.tandfonline.com/doi/full/10.1080/22221751.2024.2327385

Funding: Niedersächsisches Ministerium für Ernährung, Landwirtschaft und Verbraucherschutz , 184.786 EUR

Project Details:
The aim of the study is to begin recording the zoonotic potential of raccoon dog, nutria and raccoon populations in Lower Saxony, taking into account the distribution of these and other susceptible animal species in the region. For this purpose, a small number of animals are sampled and autopsied from the hunting grounds. This study is funded by the hunting levy of the MELV.

Funding: DAAD, 24.705 EUR

Project Details:
Aposematism and crypsis are contrasting antipredator strategies. In the color polymorphic Oophaga pumilio, phylogenetic analyses have shown that populations with cryptic and aposematic coloration might have evolved independently in different islands. Two other species, O. granulifera and O. vicentei also display cryptic and aposematic color morphs in geographically isolated populations. Particularly, phylogenetic analyses of the evolution of these contrasting antipredator strategies can improve our understanding on the evolution of polymorphism in aposematic species. This project aims to uncover the molecular signatures of selection present in the genes of three Oophaga species that experienced independently evolved cryptic and aposematic phenotypes. To this effect, we look forward to elucidate the phylogenetic relationships of the genus and quantify the variation in gene expression and allelic frequencies using state-of-the-art methods.

Results:

Cajigas Gandia A, Rodríguez A, Mantzana Oikonomaki V, Pröhl H (2024) Genomic signatures of selection for aposematism and crypsis in Oophaga poison frogs. Poster. EMBO Early Career Lecture Course "Evolutionary and Comparative Genomics" Nafplion, Greece

Cooperation Partners:

Dr. Evan Towney, Goethe Universität Frankfurt, Biologicum

Project Details:
The pathogenesis of osteochondrosis dissecans (OCD) is considered to be multifactorial in horses. A primary traumatic and ischemic-necrotic etiology have been discussed until now. The aim of the current study is to describe the nature of pathological bone structures in comparison to normal control tissue by a multiscale examination of osteochondral fragments. With the help of a hierarchical examination, further pathomechanisms are to be identified and potential etiologic factors further decribed.

Results:

Leuffert, S., Cardinaux, E., von Brackel, F., Amling, M., Geburek, F. Osteochondrale Fragmente in der Fesselgelenksregion - eine kontrollierte histomorphologische Studie. In: Tagungsband des DVG-Vet-Congress 2024 - 7. Internationaler Kongress zur Pferdemedizin / Tagung der DVG-Fachgruppe Pferdekrankheiten, 1.- 2. November 2024, Berlin, Verlag der DVG Service GmbH, Gießen, ISBN 978-3-86345-736-5, S. 49-52

Cooperation Partners:

Prof. Dr. M. Amling, Dr. F. von Brackel, Universitätsklinik Hamburg - Eppendorf, Institut für Osteologie und Biomechanik (IOBM)

Funding: BLE, 443.163 EUR

Project Details:
The objective of the project is to assess the potential of the organic rearing system for dual-purpose chicken breeds under the aspects of a resource-efficient optimized feeding and animal welfare.
The focus is on the integration of two different insect species (Acheta domesticus/n.n.) and macroalgae (Palmaria palmata/n.n.) into the feeding regimes of currently used breeds in organic farming.

Cooperation Partners:

Oekologische Tierzucht gGmbH

Johann Heinrich von Thünen-Institut

Hochschule für nachhaltige Entwicklung Eberswalde

Leibniz-Institut für Agrartechnik und Bioökonomie e. V.

Bioland Beratung GmbH