Research

Funding: DFG, 45.000 EUR

Project Details:
Evolution and ecology of RNA-viruses in small mammels

Funding: DFG, 45.000 EUR

Project Details:
Role of adipose tissue as a silent reservoir for respiratory virus replication

Funding: DFG, 250.000 EUR

Project Details:
It is well known that a number of viral pathogens can be detected in saliva of infected humans and animals. However, for most of these viruses the source of their presence in saliva and in the oral cavity remains unknown. While it has been reported that human salivary glands can be infected by SARS-CoV-2 and some other viruses, the role of salivary gland tissues in infection of pigs with respiratory and most enteric viruses has not been addressed so far. To characterize infection of porcine salivary glands by both respiratory viruses (influenza A virus, porcine respiratory coronavirus) and enteric viruses (transmissible gastroenteritis virus, porcine rotavirus A), differentiated salivary gland epithelial cells and organoid cultures from pigs were established by the group of the PI. In addition to porcine influenza viruses, human and avian influenza viruses will be used to investigate a possible role of porcine salivary glands in interspecies transmission and evolution of influenza virus.

Funding: DFG, 250.000 EUR

Project Details:
The bovine epithelia-choreal placenta protects the fetus from infections with numerous pathogens. However, some viruses, such as bovine viral diarrhea virus (BVDV) or bluetongue virus, are able to cross the placenta barrier during pregnancy. In the case of BVDV, diaplacental infection with non-cytopathogenic (ncp) viruses between the 40th and 125th day of gestation is a mandatory prerequisite for the establishment of persistent infections and is therefore of outstanding epidemiological importance. In contrast, infection of pregnant animals with cytopathogenic (cp) BVDV does not lead to the birth of persistently infected offspring.
An important aspect of the placenta's barrier function against pathogens is innate immunity. First, we want to investigate the innate immune response of polarized bovine placenta cells to dsRNA applied to either the basolateral or apical compartment. Moreover, we will examine the efficiency of viral replication and release of BVDV and other bovine viruses, and characterize the innate immune response after basolateral and apical infection.

Funding: Deutsche Forschungsgemeinschaft (DFG), 496.785 EUR

Project Details:
Paratuberculosis - Johne’s disease - is a worldwide occurring, progressive, fatal enteritis of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). The primary host tissue harboring MAP is the distal ileum, which is also the main site of zinc absorption of the host. MAP is equipped with a canonical ZnuABC zinc uptake transporter, which is also found in other mycobacterial pathogens, and two additional unique zinc uptake transporters located on the MAP-specific large sequence polymorphisms LSP14 and LSP15. Moreover, LSP14 harbors a putative zincophore gene cluster - sid - not found in other closely related or pathogenic mycobacteria, suggesting the presence of an additional zinc support system in MAP. We previously showed that this cluster is regulated zinc dependently by the Zinc uptake regulator Zur and encodes an NRPS (Non Ribosomal Peptide Synthetase), which is thought to synthesize a zincophore. In preliminary experiments, we detected for the first time a MAP zincophore candidate using metal isotope-coded profiling (MICP). Given the essential role of zinc and zincophores in bacterial survival and establishment of infection, it is of great importance to elucidate and fully understand the function of these systems in MAP zinc homeostasis and pathogenicity. The project aims to further identify, confirm and characterize MAP zincophores, to link the sid cluster to zincophore production, to elucidate of the role of sid in MAP zinc homeostasis and intracellular survival, and to investigate zincophore translocation systems. Our expected findings will contribute to the understanding of zinc homeostasis in MAP and other mycobacteria.

Cooperation Partners:

Dr. Thomas Wichard

Friedrich-Schiller-Universität Jena

Institut für Anorganische und Analytische Chemie

Lehrstuhl für Instrumentelle Analytik

Lessingstraße 8

07743 Jena

Funding: UBA, 156.832 EUR

Project Details:
Because they occupy the top of the food chain, apex predators such as birds of prey, otters, seals, and porpoises serve as useful indicators of pollutants in terrestrial, freshwater, and marine environments. When combined with data from selected prey species (e.g., fish), data from chemical monitoring of top predators can provide useful quantitative information on the persistence and bioaccumulation of chemical substances throughout the food web. A number of these chemical substances are classified as persistent, mobile, or bioaccumulative and toxic substances (PMT, PBT substances), very persistent, very bioaccumulative, and very mobile substances (vPvB/vPvM substances), as well as endocrine disruptors (EDs).
The "Beyond Life Apex" project will investigate the contamination of food chains by top predators in order to determine the presence of substances and their co-exposure in Germany, as well as the potential adverse health effects of selected contaminants. The project will provide new insights into the exposure of organisms at various trophic levels, the degree of biomagnification in terrestrial and aquatic food chains, priority substances for further regulatory assessments, the adverse effects of chemical pollutants on top predators, and the causes of these effects. This project is being carried out as a collaboration between the Institute for Terrestrial and Aquatic Wildlife Research (ITAW), the Leibniz Institute for Zoo and Wildlife Research (IZW) in Berlin, and the Helmholtz Centre for Environmental Research GmbH (UFZ) in Leipzig, and is funded by the Federal Environment Agency.

Cooperation Partners:

Helmholtz-Zentrum für Umweltforschung (UFZ)

Leibniz-Institut für Zoo- und Wildtierforschung (IZW)

Funding: Teilfinanzierung durch die Prof. Dr. Peter und Jytte Wolf - Stiftung für Epilepsie, 19.200 EUR

Project Details:
Etwa ein Drittel aller Humanpatienten und Zweidrittel aller caninen Patienten mit Epilepsien werden mit den vorhandenen Medikamenten nicht anfallsfrei. Die Entwicklung neuer Therapiestrategien gehört daher zu den großen medizinischen Herausforderungen im Bereich der Epilepsieforschung. Pharmakologische Behandlungen mit Anfallssuppressiva (Antiepileptika) sind zudem mit dosis-abhängigen unerwünschten Nebenwirkungen assoziiert, so dass neben der Entwicklung neuer Medikamente zunehmend auch nicht-pharmakologische Begleit-therapien untersucht werden. Regelmäßiges aerobes Ausdauertraining kann einen therapeutischen Einfluss auf epileptische Anfälle haben und zudem eventuell die Wirksamkeit von Medikamenten direkt beeinflussen. Die Projekthypothese ist, dass sich die antikonvulsive Wirksamkeit verschiedener Klassen von Antiepileptika durch Kombination mit geeigneten Trainingsparametern verstärken lässt, so dass eine geringere Dosis der Medikamente für die Behandlung eingesetzt werden muss, was in der Folge das Risiko unerwünschter Nebenwirkungen senken sollte. Als Nebenhypothese postulieren wir, dass die zu verifizierende Wirksamkeitsverbesserung nicht auf eine Veränderung der Plasmakonzentration des Antiepileptikums zurückzuführen ist, sondern auf Veränderungen der Rezeptoren und Kanäle im epileptischen Netzwerk.

Funding: DFG (VIPER GRK)

Project Details:
Motile cilia are microtubule-based, hair-like projections on the luminal membrane of epithelial cells in conducting airways. Through their continuous wave-like beating, they evacuate mucus secreted by goblet cells, thereby contributing to muco-ciliary clearance (MCC). In this function, motile cilia are actors of the first-line defense against inhaled pathogens. Dysregulated cilia will have a long-term effect on MCC and predispose for further diseases. Similarly, the diffuse endocrine system plays an essential role in respiratory tract imbalances. However, underlying pathogenetic mechanisms are not well understood, neither in various organs nor in the trachea and larynx. Therefore, the envisioned study will enhance our understanding of short- and potential long-term effects of SARS-CoV-2 infection in the upper respiratory tract and its associated endocrine and nervous system.

Cooperation Partners:

Institut für Virologie, Universität Münster,

Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, U.S.A (Klaus Schughart),

Helmholtz-Zentrum für Infektionsforschung (HZI), Braunschweig (Robert Geffers),

Medizinisch Hochschule Hannover (Peter Claus)

Funding: DFG (VIPER GKR)

Project Details:
This project aims to investigate the effect of an early (3 days post infection [dpi]) and a late (8 dpi) adoptive transfer of green (GFP) and red fluorescent (RFP) T- cells on the microglial morphology and transcriptomic data in TMEV- infected OT-I and OT-II mice. The contribution of CD8+ and CD4+ T cell subsets for viral clearance and course of clinical disease will be investigated individually as well as the general pathomorphology and immune response with special focus on microglia morphology and transcriptomic data.

Cooperation Partners:

Institut für Neuroimmunologie und Multiple-Sklerose-Forschung der Universitätsmedizin Göttingen

Funding: DFG (VIPER GRK)

Project Details:
Characterizing the impact of morbilliviruses upon innate responses and the integrity of respiratory epithelial cells.
-Generation and characterization of 3D-culture systems of different wildlife carnivore species
-Analyses of morbillivirus infections upon respiratory tract cells of wild carnivores in vivo and ex vivo