Research

Funding: Nds. Ministerium für Wissenschaft und Kultur, 218.996 EUR

Project Details:
Ziel des Projektes "Future-VET B2" ist, neben der praxisnahen Ausbildung der Studierenden der Tiermedizin, Dienstleistung und Forschung der Transfer der Forschungsergebnisse in die Fachwelt und Öffentlichkeit. Die Maßnahme "Future-VET 2B" hat dabei das übergeordnete Ziel die Lebensmittelproduktion im Hinblick auf die Umweltauswirkungen und die Ernährungssicherheit für die wachsende Weltbevölkerung zu optimieren. Insekten können hierbei sowohl im Sinne der Kreislaufwirtschaft zusätzliche, wertvolle Futtermittel und Lebensmittel darstellen. Zudem bieten sie die Möglichkeit bei Vorliegen bestimmter funktioneller Eigenschaften als Futtermittel sowohl die Gesundheit von Tieren im Sinne der Verwendung von Futtermitteln für besondere Ernährungszwecke (VO (EU)2020/354) zu fördern, als auch nach entsprechender Modifikation eine Prüfung als Futtermittelzusatzstoff mit einer funktionellen Wirkung im Sinne der VO (EG) Nr. 1831/2003 nach Vorgabe der VO (EG) Nr. 429/2008 zu durchlaufen. Im Rahmen dieses Teilprojektes soll die bestehende Insektenzucht an der TiHo erweitert werden, um alternative Proteinquellen für Tier und Mensch zu erschließen, die
(1)Zusätzlich eine Sonderfunktion im Hinblick auf bestimmte gesundheitsbezogene Ernährungszwecke für das Tier (ParNuts in Analogie zu VO (EU) 354/2020) haben,
(2)Zusatzstofffunktion gemäß VO (EG) Nr. 1831/2003 erfüllen sollen und natürlichen Ursprungs sind und
(3)Am Ende des Weges sollen die bevorzugten Insektenarten als Novel Food (VO (EU) 2015/2283) auch Funktionen erfüllen können, die der nationalen Ernährungsstrategie der Bundesregierung und der Nationalen Reduktions- und Innovationsstrategie für Zucker, Fette und Salz in Fertigprodukten entsprechen.
Hierfür werden stufenweise, systematisch entsprechende Vorarbeiten durchgeführt, die die Möglichkeit einer Nutzung bzw. Bausteine einer Marktzulassung als alternative Proteinquelle für Tiere, Futtermittel mit bestimmten gesundheitsbezogenen Ernährungszwecken (ParNuts), Futtermittelzusatzstoff oder Novel Food ermöglichen bzw. werden sollen.

Funding: cofinanziert durch die Europäische Kommission, 107.187 EUR

Project Details:
This project aims to address a critical gap in neurotoxicity assessment by developing a novel in vitro methodology specifically targeting myelin toxicity—a decisive factor influencing peripheral sensory and motor functions. Building upon established modes-of-action (MoA) in adult neurotoxicity, the study utilizes human induced pluripotent stem cells to differentiate into mature motor and sensory neurons, along with Schwann cells. Distinguishing itself from existing in vitro methods, the project focuses on myelin toxicity, an unexplored MoA not yet incorporated into existing approaches, thereby influencing neurotoxicity assessment.
Acknowledging the regulatory imperative for swifter and more human-relevant neurotoxicity evaluations, the project aims to deliver an effective myelin toxicity assessment method. The methodology involves co-cultivating sensory or motor neurons with Schwann cells in both 3D spheres and 2D configurations. The plan encompasses characterizing cell types and scrutinizing myelin formation through immunocytochemical stainings and RT-qPCR after 4-8 weeks in culture. A pivotal aspect of the study is the exploration of optimal conditions for high-throughput testing.
Milestones include achieving the expression of neuron and Schwann cell markers, determining the optimal 2D or 3D setup for automated high-throughput myelin quantification, and scientifically validating the test method. The ultimate objective is to furnish a robust tool for assessing myelin toxicity, utilizing a compound training set.
In conclusion, this project pioneers an approach to address the gap in myelin toxicity testing within in vitro neurotoxicity assessment. By leveraging human induced pluripotent stem cells and advanced co-culture techniques, the study aims to make a substantial contribution to the development of a more comprehensive and effective neurotoxicity evaluation testing battery for regulatory use.

Results:

https://www.eu-parc.eu/

Funding: Gefördert durch die Bundesanstalt für Landwirtschaft und Ernährung Bonn/BMEL, 369.000 EUR

Project Details:
Der innovative Ansatz dieses Projektes zielt darauf ab, aus der Produktionskette isolierte Phagen als nachhaltige prophylaktische Maßnahme in der Geflügelproduktion zu etablieren.
Es sollen im Rahmen eines Zweistufenkonzepts maßgeschneiderte Phagenprodukte entwickelt werden.

Cooperation Partners:

Tierärztliche Gemeinschaftspraxis WEK, Miavit GmbH

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, 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: 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: Ministerium für Energiewende, Landwirtschaft, Umwelt, Natur und Digitalisierung , 350.135 EUR

Project Details:
After unexpected problems occurred during the data collection in the field, an objectively evaluable data basis will be created, aming at evaluation of the acoustic deterrence system. In addition to the working task, further analyses will be carried out to assess the management measures developed and implemented to date outside the public swimming area, which include, for example, the previously established protection zones or the panoramic path. In order to ensure an effective management, regular evaluation and possible optimization is essential. The counting data collected on Helgoland by Jordsand / Dünen-Ranger represents an extremely important data basis for this. Based on an extremely important data basis for this juvenils, a corresponding evaluation of the effectiveness of the measures will be carried out.
In order to investigate the temporal and spatial use of areas by grey seals in the North Sea in more detail and also to create the data basis for a tailor made management, individual grey seals will be captured on Helgoland and tagged with telemetry devices. Vocalizations of grey seals associated with mating will be recorded underwater to identify areas used for mating. In this context, a comprehensive health monitoring of grey seals will also be conducted to update knowledge on the zoonotic potential of pathogens present in grey seals for residents and tourists on Heligoland.
Additional management needs have arisen in recent years regarding the locations of grey seal births. As it repeatedly happened that single pups were born on the main island, beaches had to be closed for residents and tourists during the pupping season. At the same time, these beaches are the only places on Helgoland where dogs can run free. Thus, there is a great interest in directing the births of grey seals away from the main island, if nature conservation compatibility can be guaranteed in the process. This project will continue to investigate the extent to which the main island is already relevant during mating season.
The following questions will be addressed in the targeted project:

1) Can a seal exclusive zone be created by using an acoustic fence in the swimming area of the Helgoland dune?
2) How effective are the applied management measures on Helgoland and how can they be further optimized?
3) Which areas are used by grey seals and what are their functions? Which zoonotic pathogens do living grey seals carry on Helgoland and what danger do they pose to humans?
4) Are there possibilities to direct the locations of grey seal births?

The work packages represent the planned work required to answer the respective questions.

1) Sound exposure of grey seals in the swimming area of the Helgoland Dune.
2) Evaluation of the collected daily count data
3) Acoustic monitoring, health monitoring, and tagging of grey seals at Helgoland Dune.
4) Development of tailor made methods to keep away grey seals from main island beaches during the pupping season.

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: 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: VolkswagenStiftung, 700.000 EUR

Project Details:
Avian influenza in humans is associated with pneumonia, inflammation and high case fatality rates. We identified CYP19A1 as a key gene involved in sex-specific lung inflammation in SARS-CoV-2 infected hamsters and humans. CYP19A encodes for the aromatase enzyme that converts testosterone-to-estradiol leading to the activation of various estrogen-regulated pathways associated with lung inflammation. Treatment of SARS-CoV-2 infected hamsters with letrozole, a clinically approved CYP19A1 aromatase inhibitor, recovered impaired lung function and overall lung health in males. We further found that also avian H7N9 influenza virus infection mediates massive upregulation of CYP19A1 in the lung of infected animals. Thus, we hypothesize that estrogen-regulated activation of inflammatory pathways in the lung play a crucial role in severe viral disease outcome. Therefore, in this proposal, we will systemically evaluate the impact of compounds that inhibit the synthesis of estrogens (using aromatase inhibitors) or interfere with estrogen-regulated down-stream pathways (using estrogen antagonists, SERMs, SERDs) against avian influenza in the hamster model. Obtained data will provide new insights into estrogen-mediated inflammatory pathways upon infection with respiratory viruses. Moreover, identification of common pathways might result in overarching drug targets to treat inflammatory lung diseases in general.

Cooperation Partners:

Evotec