Research

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.

Project Details:
The aim of this project is the development and adaptation of AI-based methods for automated annotation and functional interpretation of single-cell sequencing data in mammals. The focus is on adapting transformer-based models to multi-species datasets from livestock and model organisms. By integrating single-cell transcriptomic data, robust models for cell type annotation, state classification, and regulatory effect prediction will be established. The developed approaches will be applied to tissues with growth-related processes to identify functional cell populations and regulatory patterns using AI. The objective is to provide scalable tools for comparative functional genomics at single-cell resolution in mammals.

Project Details:
The aim of this follow-up project is to investigate the contribution of structural genomic variation to the genetic architecture of growth in the pig model. The focus is on the identification and characterization of structural variants using long-read sequencing and their regulatory effects in non-coding genomic regions. Analyses of animals with divergent growth phenotypes will be used to detect growth-associated structural variants and selection signatures. These variants will be evaluated with respect to their location in regulatory sequences, putative enhancers, and chromatin domains, and linked to gene expression data from growth plate tissue. The objective is to identify functionally relevant non-coding variation affecting growth-regulatory processes.

Cooperation Partners:

Prof. Tim Kacprowski, Leiter Abteilung Data Science in Biomedicine, Peter L. Reichertz Institut für Medizinische Informatik der TU Braunschweig und der Medizinischen Hochschule Hannover

Funding: DFG, 535.000 EUR

Project Details:
When dry preservation of gametes and/or genetic material were possible without loss of fertilizing potential, this can be implemented for securing genetic resources and would transform biobank facilities and the breeding industry. This would facilitate low-cost room temperature storage easing off-the-shelf availability and transport. Moreover, dry preservation methods for biologics can be implemented in underdeveloped countries, remote locations, and non-laboratory settings. Without taking protective measures, biomolecules in mammalian cells are subject to (irreversible) conformational changes during drying and specimens are prone to chemical degradation during storage, impairing their functions. Numerous attempts have been pursued to preserve cell viability and functionality in the dried state, mostly inspired by nature’s way to survive drying in a state of suspended animation referred to as anhydrobiosis. However, only limited successes have been reported in keeping ordinary mammalian cells viable after drying and subsequent rehydration. Attempts focused on the introduction of specific disaccharides (i.e., trehalose, sucrose), stress proteins, and membrane modification strategies, which play a role in acquiring desiccation tolerance in nature. However, the complex orchestrated cellular adaptation mechanisms of anhydrobiotic organisms are not likely to be mimicked in cells that are not naturally resistant to dehydration. Dried mammalian cells may retain their structure and specific functional properties. For example, dried sperm and somatic cells can be injected into (enucleated) oocytes for the production of offspring. However, under ambient conditions, biomolecules in dried cells are susceptible to rapid degradation during storage. Major factors impairing storage stability of biomolecular structures in a dried cellular environment are the presence of reactive molecules, environmental conditions, and inherent susceptibility for damage (e.g., degree of lipid saturation and chromatin condensation). We propose a different approach for long-term room temperature preservation of genetic resources; not focusing on recovering fully functional cells but by generating ‘artificial’ cell-like nuclei-containing structures. We plan to do this by (1) making ‘ghost cells’ from sperm to remove damaging reactive molecules normally present in the cells, while keeping organelles and cytoskeletal elements inside, and (2) by making demembranated sperm encapsulated in giant liposomes. In both cases, damaging reactive molecules in cells are removed, while protective molecules can be easily introduced.

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

Project Details:
Charakterisierung Darmflora und deren Einfluss aus das Immunsystem bei Reptilien