Research

Funding: MEKUN, 229.320 EUR

Project Details:
Pressures on harbor porpoise habitat in the Schleswig-Holstein waters of the North Sea and Baltic Sea continue to increase due to anthropogenic activities. These include offshore wind turbine construction, Fehmarn Belt crossing, military and civilian blasting (munitions waste), fishing, as well as the use of PAL systems, tourism activities, chemical and pharmaceutical pollution, garbage, habitat loss, and other disturbances.
Studies of reproduction and age structure of harbor porpoises found dead in the waters of Schleswig-Holstein have shown that the animals generally die very young and that females in particular have little time to reproduce. The age structure of dead found animals provides evidence that many females die before or shortly after reaching sexual maturity. In addition, an increased number of pregnant females was found dead in the year 2021. Further data collection is needed to develop relationships that may contribute to reverse this trend. Initial studies on hearing and contaminant exposure in harbor porpoises have additionally shown that some of the animals are exposed to significant levels of persistent organic pollutants (POPs) and mercury, and hearing damage is evident in some animals. The relationships between hearing damage and exposure to contaminants as well as their significance at the population level, require further investigation. Systematic surveys of harbor porpoises are extremely important to assess trends in baseline biological data (age, sex, weight, location, date of discovery, species), as well as health status and causes of death. These data are elementary as they are reported to ASCOBANS, ICES, HELCOM, OSPAR and the IWC.
Within the framework of the project, freshly dead harbor porpoises from the Schleswig-Holstein North Sea and Baltic Sea will be examined in detail for their state of health. Histological, immunohistochemicaland microbiological examinations will be performed. The parasite fauna and its prevalence can give important information about its influence on the harbor porpoise, but also on the whole ecosystem in the Baltic Seaas intermediate hosts are important for transmission in different trophic levels. These additional investigations shall be used for the assessment parameters in the North Sea and Baltic Sea for the development of GES (Good Environmental Status) in the future and applied for OSPAR, HELCOM and the Marine Protection Framework Directive. In particular, if harbor porpoise mortalities become more frequent, immediate investigations are to be conducted to shed light on the possible causes and to uncover correlations. Based on the results, recommendations are to be developed regarding areas with increased potential for conflict and thus a further requirement for habitat investigations. Ears from well preserved animals found dead will also be collected and made available for further studies to examine the changes occuring in bycatch compared to animals found dead as well as to assess the effects of blasting, acoustic and chemical exposure. Similarly, post mortem examinations will be used to take collect samples for toxicological studies that can be analyzed as part of further projects.

Funding: UBA/BFG, 350.135 EUR

Project Details:
In the European Union, biocides are officially approved following the EU Biocide regulation No. 528/2012. So far, the following eight anticoagulants were assessed and approved for rodenticide use in the EU: Warfarin, Chlorophacinone, Coumatetralyl, Bromadiolone, Difenacoum, Brodifacoum, Difethialone and Flocoumafen. The first three active ingredients belong to the first-generation anticoagulants, whereas the last five belong tot he second-generation anticoagulants. Second-generation anticoagulant rodenticides (AR) were considered persistent, bioaccumulative and toxic (PBT- or vPvB ingredients) and thus only approved for pest control under very strict regulations, due to the lack of alternative ingredients.

Taking into account the results of previous research projects to investigate the contamination of ARs in fish and the effects of Ars on the aquatic environment, this project aims to evaluate the effectiveness of current risk mitigation measures to reduce contamination of water bodies with Ars by using a biota monitoring approach. A nationwide, strategic monitoring for otters (Eurasian otter, Lutra lutra) will be initiated to evaluate current risk mitigation and to determine relevant exposition for both aquatic and semi-aquatic top predators. In addition, the transfer of active ingredients alongside the aquatic food chain and the metabolism of Ars in fish will be investigated.

The outcome of the project with regards to environmental contamination of aquatic habitats with Ars and the effectiveness of current risk mitigation measures shall allow the funding agency to implement scientifically based decisions in the biocide registration. Also, former decisions might be revised or substantially improved.

Funding: MEKUN, 132.092 EUR

Project Details:
Grey seals are increasingly found on both the North Sea and Baltic Sea coasts of Schleswig-Holstein, indicating that the number of animals using these waters is continuing to rise.
The increasing populations also increase the urgency of examining these marine mammals for their health status, as it is suspected that they can play a role in the spread of infectious diseases of harbor seals such as distemper, particularly due to their extended migratory behavior. In addition, individual animals with severe disease processes are repeatedly recorded in the Baltic Sea. In both waters, it is particularly important to examine the animals for their health status as carriers of zoonotic diseases, especially as people have been infected with these pathogens through contact with carcasses in the past. Furthermore, potential anthropogenic influences on disease incidence must be investigated in order to protect the seal populations.
With increasing populations, attacks by gray seals on other grey seals, harbor seals and harbor porpoises are also on the rise. This can occur through predation, but also through sexual intercourse with harbor seals as well as juvenile grey seals of both sexes. Negative population effects are possible as well as effects on the health of the marine mammal-eating grey seals, as they hunt at a higher trophic level than their conspecifics, comparable to polar bears or orcas. Initial cases of influenza in both harbor seals and grey seals have shown that seals are susceptible to this virus and need to be studied closely both as a reservoir and as a "spillover" of this potential zoonosis. In addition, anthropogenic activities in the habitat of grey seals continue to increase, which can have various influences not only on the health status but also on the habitat use of the animals.
The aim of this research project is to investigate the health status and causes of death of grey seals that died in the waters of Schleswig-Holstein. The aim is to examine whether the parasitic, viral and microbial load of grey seals, in particular zoonotic pathogens, is changing. For this purpose, the grey seals, which will be recovered in the years 2023 to 2026 and brought to the ITAW for examination, will be completely dissected. Histological, parasitological, virological and microbiological examinations will be carried out. In addition, a comparison will be made with the results from previous years in order to assess the development of the health status.
The development of grey seal populations in the North Sea and Baltic Sea will also be researched and evaluated. As grey seals are highly mobile marine mammals, data will be exchanged with neighboring countries. The Trilateral Wadden Sea Secretariat (CWSS) and the Trilateral Marine Mammal Expert Group (EGMama), as well as HELCOM's Marine Mammal Health Group for the Baltic Sea region and OSPAR's Marine Mammal Working Group in the North Sea, play a special role here. The results of the investigations are urgently needed for the work on the Marine Protection Framework Directive and the aforementioned agreements.

Funding: Umweltbundesamt, 306.051 EUR

Project Details:
Plastic pollution is now known worldwide and is an omnipresent problem for every ecosystem. In 2021, the annual plastic production was 390.7 million tonnes. A distinction is made between macroplastics (> 5 mm), microplastics (MP; < 5 mm) and nanoplastics (in the nanometre range).
These plastic particles enter the marine environment via various routes, e.g. via wastewater, atmospheric transport, ocean currents, landfills and fishing activities. Once in the environment, macro litter is broken down into smaller particles because the polymer structure is weakened by photodegradation (UV), hydrolysis, mechanical abrasion, biodegradation (microorganisms) or biofouling (colonisation of plastics by microbes).
The polar regions were long considered to be largely unaffected by humans. Even though it is not a heavily populated region, MP has been detected in this ecosystem in a variety of compartments such as the water column, snow, sea ice and deep-sea sediments. The increase in temperature as a result of climate change and the associated melting of ice is causing various problems - in addition to the rise in sea level, the increasing decrease in sea ice is leading to the release of microplastics that were previously bound by the ice deposits. This is now "available" and enters the sensitive ecosystem - the consequences cannot yet be estimated. The presence of microplastics in the Arctic means that species in the polar region are now increasingly confronted with an anthropogenic problem - the presence of marine litter or microplastics and its consequences. This also includes Arctic peoples, whose diet also includes the meat and fatty tissue of marine mammals.
The aim of the project is to obtain valid data on microplastics and associated pollutants in marine mammals from Arctic waters and thus improve the state of knowledge in this sensitive habitat. The acquired knowledge is the basis for future trend analyses that are necessary to enable effective MP monitoring in Arctic waters. The following species characteristic of the Arctic will be studied: harbour porpoise (Phocoena phocoena), ringed seal (Pusa hispida), grey seal (Halichoerus grypus), harbour seal (Phoca vitulina), hooded seal (Cystophora cristata), bearded seal (Erignathus barbatus) and polar bear (Ursus maritimus). Another important aspect is the establishment of a method for visualising MPs in tissue. For this purpose, pieces of tissue from the gastrointestinal tract are prepared and examined both histologically and using a confocal microscope. Various staining techniques are then used to identify potential microplastics in the tissue. This is an important step towards better understanding the transport routes of microplastics and verifying entry paths.
The samples come from various co-operation partners such as the University of Iceland and the Norwegian Polar Institute. The pollutant analysis is being carried out by the University of Siena.

Funding: MWK Niedersachsen, 184.200 EUR

Project Details:
Die Kryokonservierung von ex vivo und in vitro Kultursystemen des Respirationstraktes verschiedener Spezies ist eine bislang wenig erforschte Methode, welche den Nutzen dieser Modelle als Ersatz und Ergänzung von Tierversuchen aber deutlich steigern könnte. Daher sollen im vorliegenden Teilprojekt primäre Zell- und Gewebekulturen wie Nasenschleimhaut-Explantate, Air-Liquid Interface Kulturen aus trachealen Epithelzellen und Lungenpräzisionsschnitte von ausgewählten Spezies wie Frettchen, Hund, Maus und Schwein mittels verschiedener Gefriermedien kryokonserviert und nach dem Auftauen morphologisch, funktionell sowie anhand einer Transkriptomanalyse untersucht und mit nicht kryokonservierten Kulturen verglichen werden. Insbesondere die Zilienmorphologie und funktionalität der Kultursysteme soll dabei im Mittelpunkt stehen und durch softwaregestützte Videoanalysen näher charakterisiert werden. Die gewonnenen Erkenntnisse sowie die generierten Kulturen sollen Projektpartnern des Verbundes und darüber hinaus anderen Arbeitsgruppen über die gesamte Förderperiode zur Verfügung stehen.

Cooperation Partners:

Forschungskooperation mit der Medizinischen Hochschule Hannover: "Mikro-Replace-Systeme"

Funding: DFG, 372.000 EUR

Project Details:
Der Begriff "innate immune memory" beschreibt das Phänomen, dass Zellen des angeborenen Immunsystems auf ein Pathogen oder ein Pathogen/Mikroben-assoziiertes molekulares Muster (PAMP/MAMP) anders reagieren, wenn sie vorher Kontakt mit diesem PAMP oder anderen Pathogenen hatten. Die stärkere Sekundärreaktion wird als Ausdruck eines Trainings des angeborenen Immunsystem oder als "trained innate immunity" bezeichnet, deren Induktion ein vielversprechendes prophylaktisches Konzept darstellt. Um dies für das Rind nutzbar zu machen, fehlen entscheidende Grundlagenkenntnisse über die Biologie relevanter, zu trainierender Immunzellen: die Monozyten und die aus ihnen differenzierenden Makrophagen. So ist noch unbekannt, inwieweit das hormonelle Profil und zirkulierende Stoffwechselmetaboliten von Kühen unterschiedlicher Leistungs- und Reproduktionsstadien die Monozyten/Makrophagen-Differenzierung und Polarisierung beeinflussen und wie dies das Reaktionsverhalten auf eine Stimulation mit Erreger-stämmigen Molekülen steuert und ihr innate immune training beeinflusst. Vor diesem Hintergrund soll im Projekt analysiert werden, wie sich die Zusammensetzung boviner monozytärer Subpopulationen, deren Transkriptom, das Expressionsmuster von C-Typ-Lektin-Rezeptoren (CLRs) und ihre Trainierbarkeit durch CLR-Liganden im Verlauf der Trächtigkeit und in verschiedenen Leistungsstadien verändert und gesteuert wird. Ergänzt wird dies durch mechanistische Analysen von epigenetischen Modifikationen und Effektorfunktionen myeloider Zellen nach innate immune training über CLR-Liganden. Die Analysen des CLR-vermittelten Trainings und der Monozyten/Makrophagen-Polarisierung erfolgen bei Kühen in den zentralen Lebensphasen, der Hochlaktation und der Spätträchtigkeit, um zu prüfen, wann bei der Kuh Differenzierungs-steuernde immunmodulatorische Strategien Wirksamkeit zeigen, die auf dem innate immune training-Prinzip beruhen. Im Projekt werden grundlegende Erkenntnisse über die CLR-abhängige Modulation von Monozyten- und Makrophagen-Funktionen gewonnen, die in der Prophylaxe peripartaler Infektionserkrankungen und im rationalen Design Leistungs-angepasster immunmodulatorischer Konzepte Anwendung finden können.

Funding: The International Human Frontier Science Program Organization (HFSP), 1.106.000 EUR

Project Details:
Insect cell membranes differ from mammalian membranes by deformability, lipid content and distribution. Enveloped insect-borne viruses require intimate interactions with cellular
membranes to enter cells, replicate their genomes in cells and bud from cells. Despite fundamental biophysical differences between insect and mammalian membranes, viruses can productively infect cells from both phyla. Decades of studies on insect-borne viruses have not addressed the machinery of insect membrane deformation and its exploitation by viruses. Working at the interface of insect genetics, biophysics and infection biology, our newly formed team has assembled innovative technologies to break through this barrier in the field. Through the combined expertise of the PIs, we will: 1. Employ gene editing libraries in insect cells to identify host factors steering virus - membrane interactions; 2. Image membrane deformation at high resolution; 3. Assess the impact of membrane deformation on permissiveness to insectborne viruses. These studies will provide insight into mechanisms driving insect membrane shape and revolutionize our understanding of virus adaptation across fundamentally different
species.

Cooperation Partners:

Dr. Nicholas Ariotti, Institute for Molecular Bioscience, Australia

Dr. Norbert Perrimon, Harvard Medical School, USA

Funding: DFG, 498.400 EUR

Project Details:
The equine recurrent uveitis (ERU) is the main reason for blindness in horses, and 10% of the european horses are affected. Significantly, ERU is an important available model for human autoimmune uveitis as the clinical and immune-pathological characteristics are similar. As a cause for ERU, various hypotheses are described in the literature. On the one hand, infections with Leptospira interrogans are discussed as well as other bacterial, parasitic or viral infections. Independent of the initiating cause, there are numerous indications that ERU is an immune-mediated disease. In the body after the control of the primary infection, an overreaction of the immune system occurs in response to activated immune cells. In addition to lymphocytes, these immune cells can also be neutrophil granulocytes. Among various antimicrobial functions, neutrophils have been shown to release neutrophil extracellular traps (NETs). NETs are extracellular DNA fibers with associated proteases and antimicrobial peptides which are released by activated cells. NETs mediate entrap of invading pathogens, but when massively released may contribute to detrimental autoimmune reactions of the host.
The research project presented here is intended to provide essential insights for the involvement of NETs in the pathogenesis of ERU. In the first phase of our study, our findings indicate an involvement of NETs in the pathogenesis of ERU with detrimental effects. In short, NETs correlate to disease severity, seem to damage the blood retinal cells, and induce autoantibodies against NET proteins. We hypothesize, that those autoantibodies might shield the NETs from degradation by DNases, resulting in their persistence and potentially in new disease episodes. Thus, in the current project we aim to characterize if and how the phase of disease (non-active quiescent phase versus acute inflammatory phase) influences cellular involvement and extracellular DNA release. Based on our previous data, we further hypothesize that different cell types besides neutrophils play a role in extracellular DNA release during the progression of ERU, which enables crosstalk between various immune cells. Therefore, we will study the release of ETs by other immune cells besides neutrophils and its interplay with adaptive immune cells. Finally, since the use of gentamicin in the treatment of ERU patients is well established, the aim is to determine the influence of gentamicin in varying concentrations and along with distinct stimuli on equine immune cells, focusing on ET release.
&#8195;

Funding: Niedersächsisches Ministerium für Wissenschaft und Kultur (MWK), 324.000 EUR

Project Details:
The aim of this subproject is the further development and optimization of a 3D lung epithelial cell culture model
for the investigation of viral and bacterial infections and the effect of immunomodulatory
immunomodulatory substances on the course of infection and cell biochemical processes. An increased
complexity of the model system using physiological or pathophysiological oxygen
conditions and microfluidic systems enables the in vitro system to be approximated to the in vivo situation and
to the in vivo situation and will help to reduce the number of test animals in the long term. The
complexity of the infection model is reduced by physiologically relevant oxygen conditions (defined
tissue-specific hypoxic conditions) and by 3D co-cultivation of human or animal pulmonary
or animal pulmonary epithelial cells and neutrophil granulocytes. In addition
the use of primary cells and induced pluripotent stem cells should provide long-term optimization.

Funding: Bundesministerium für Bildung und Forschung, 625.000 EUR

Project Details:
As long as animal experiments cannot be completely replaced, the question will arise on which animals research should take place. In this project, an interdisciplinary working group wants to investigate the ELSA-relevant question, according to which criteria the selection of laboratory animal models takes place or should take place. The aim of the enterprise is to determine the manifold reasons for the choice of certain laboratory animals; the process is interdisciplinary in the full sense of the word and put the different rationalities into a well-founded correlation. The question condenses several open and important issues concerning the treatment of animals. The answer is to be examined in each of the disciplines involved, between them and finally in their association, whether it is possible to establish a coherent catalog of criteria that also creates clarity for the practice of animal experimentation, both for everyday research and at the interface to legislation and enforcement. This is important against the background of rapidly changing social value judgements about animals, which also lead to permanent tensions here. In this project we want to investigate the ELSA-relevant question of the criteria for the selection of laboratory animal models. We follow an interdisciplinary approach, which is represented by the following cooperation partners: Its members are: Prof. Dr. Peter Kunzmann (ethics), Prof. Dr. Bernhard Hiebl (laboratory animal science), Prof. Dr. Maren von Köckritz-Blickwede (infection research) (all TiHo- Hannover) and the legal scientist Prof. Dr. Dr. Tade Spranger (University of Bonn).

Cooperation Partners:

Tade Spranger, Rechts- und Staatswissenschaftliche Fakultät, Bonn