Overview of research projects

Funding: Deutsche Forschungsgemeinschaft DFG, 401.271 EUR

Project Details:
Infectious bursal disease virus (IBDV) is one of the most important immunosuppressive chicken pathogens worldwide. Despite vigorous vaccination, IBDV field outbreaks occur. This project will investigate the role of different immune cell populations in infectious bursal disease pathogenesis and will address specifically the impact of age and genotype in this context. We will therefore contribute to the overall improvement of chicken health and welfare, and in addition may inform development of new farm animal vaccination strategies. The project is embedded in the DFG-research group "ImmunoChick".

Cooperation Partners:

PD Dr. Angela Berndt, FLI

PD Dr. S. Härtle, LMU München

Dr. T. von Heyl, TU München

Dr. S. Früh, FU Berlin

Prof. Dr. B. Kaufer, FU Berlin

Dr. El-Sayed Abdel-Whab, FLI, Riems

Prof. Dr. B. Schusser, TU München

Prof. Dr. J. Kaufman, University of Edinburgh

Project Details:
Nanotechnology is a fast-moving area that finds applications in such diverse areas as material science, electronic engineering, consumer goods production, medicine, and agriculture. A recent innovation in the field is the use of plant extracts in nanoparticle synthesis. Due to the involvement of auxiliar natural substances, this so called "green nanotechnology" aims for environmentally beneficial and more biocompatible nanoparticles free from hazardous substances. Copper nanoparticles (CuNPs), synthesized using green methods, have been particularly noted for their potent insecticidal activity. On the other hand, there is a growing public awareness about the toxic potential for humans associated with nanoparticles applied to the environment. The small size of nanoparticles poses the risk of permeating the protective blood brain barrier into the nervous system, even by inhalation through the nose. The nervous system, and in particular the developing central nervous system is more sensitive to damage than other organs. Whereas developmental neurotoxicological testing usually employs large numbers of mammalian experimental animals, basic mechanisms can be studied in cell culture, or insect embryonic tissue culture.
The purpose of the project is the development of a joint multidisciplinary approach to study potential adverse effects of green-engineered nanoparticles on the developing nervous system. On the biological side, using neuronal precursor cells and/or embryonic insect nervous tissue, the effect of nanoparticles can be tested on neurotoxicological endpoints such as cell differentiation, neurotransmitter content, cell migration, neurite outgrowth, and growth cone navigation. On the material science side, modification of the production process enables to test effects influenced by nanoparticle size, biochemical modification, or effectivity of uptake.
The objective of this collaboration is to define a specific project in which the strengths of both partners, development of green-engineered nanoparticles in South Africa, and developmental neurotoxicology in Germany, are combined to gain deeper knowledge about the interaction of these new materials with living cells, connecting the distinct fields of human and environmental nanotoxicology.

Results:

Stern M, Botha N, Cloete KJ, Maaza M, Tan S, Bicker G (2024) Neurotoxicity and developmental neurotoxicity of copper sulfide nanoparticles on a human neuronal in vitro test system. Int J Mol Sci 25 (11): 5650. https://doi.org/10.3390/ijms25115650

https://doi.org/10.3390/ijms25115650

Cooperation Partners:

Dr. Karen Jacqueline Cloete, University of South Africa/iThemba Laboratory for Accelerator Based Sciences - National Research Foundation: Somerset West, Western Cape, South Africa

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 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

Funding: DFG (VIPER GRK)

Project Details:
Hypothesis:
Viral genomic sequences obtained from archived canine formalin-fixed, paraffin embedded tissue of the central nervous system and will allow establishing a cause-consequence relationship between the detected known and unknown viral pathogen and pathological findings.
Aim and objectives:
The general aim of the project is further identify the viral cause of canine diseases of the central nervous system.
-By using conventional histology and immunochistochemistry of archived tissues from the last 6 decades to identify cases of non-supprative encephalitis of unknown origin
-Suspected virus infection will be further substantiated by applying double-stranded RNA or selected interferon stimulated genes specific antibodies and a probe specific for interferon β.
-Followed by ribonucleic acid extraction from the selected FFPE tissues, RT-qPCR using pan-genus primer and/or NGS. Alignment to reference genomes available in databases will be used to detect known viral pathogens and related unknown viruses
-Investigation of the pathogenesis of the discovered virus by studying cell tropism and the distribution of the virus in the host organism using in situ hybridization for the distribution of the pathogen

Cooperation Partners:

Institut für Virusdiagnostik, Friedrich Löffler Institut

Funding: DFG, 45.000 EUR

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

Funding: DFG, 45.000 EUR

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

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: DFG, 45.000 EUR

Project Details:
Glycoprotein-mediated immune evasion mechanisms of human and animal pneumoviridea