Overview of research 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: 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.
 

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

Project Details:
At Hofgut Neumühle, data on the health and performance of dairy cows is continuously collected and stored in various electronic data management systems. Scientific questions repeatedly arise that should be clarified with the help of an analysis of the available data (so-called secondary data analysis). Before this data analysis is possible, an overview of the available data sources, the primary collection objectives, the data contained and the metadata describing the existing data should be drawn up.
To this end, the origin of the data is first traced on site and the (original/primary) purpose for which it was collected is understood and documented. Extracts from the data sources are created to serve the creation of the above-mentioned over-view. These excerpts will be further analyzed using application examples. As an important aspect of the work, the implications for subsequent secondary data analyses will be presented and discussed (Translated with DeepL.com (free version)).

Cooperation Partners:

Hofgut Neumühle (Theresa Scheu)

Funding: Bundesministerium für Ernährung und Landwirtschaft (BMEL), 164.593 EUR

Project Details:
The aim of "InUtero" is to develop a lifelike simulator for midwifery in small ruminants and to implement this model in teaching and training. The Clinical Skills Lab, together with the Clinic for Small Ruminants, is responsible for the development and validation of the simulator as well as the preparation of detailed instructions. The animal husbandry school at the Triesdorf Agricultural Training Institute and the Echem Agricultural Training Center will use and evaluate this simulator as part of the obstetric teaching of their trainees as well as in the context of seminars and workshops in adult education. The close cooperation between the project partners enables the simulator to be constantly adapted and modified so that at the end of the project phase there is a lifelike simulator for midwifery in small ruminants that is optimized to meet the demands and needs of both teachers and learners.

Cooperation Partners:

Landwirtschaftliches Bildungszentrum Echem

Landwirtschaftliche Lehranstalt Triesdorf

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: Bundesministerium für Ernährung und Landwirtschaft (BMEL), 365.439 EUR

Project Details:
Ziel des Projektes "CalPhy" ist es, das Auftreten von behandlungsbedürftigen Erkrankungen in der Kälberhaltung zu reduzieren und damit erhöhten Verlusten entgegen zu wirken. Durch den Einsatz von hochwertigen Ergänzungen soll insgesamt die Versorgung der Kälber verbessert und damit die Tiergesundheit, das Tierwohl und die Leistung gefördert werden. Gezielt soll für die besonders empfindlichen Tiere innerhalb der Tiergruppen ein teil-individualisiertes Fütterungskonzept für die Praxis entwickelt werden. Leichte und in Teilen auch in gut geführten Beständen durch unvermeidbare Situationen (mechanische Geburtsprobleme etc.) geschwächte Neugeborene, sind besonders betroffen von einer ungenügenden Kolostrumversorgung. Diese Kälber benötigen zusätzlichen Schutz, damit die Gefahr eines überdurchschnittlichen Abfalls des kolostralen Immunschutzes nicht die Infektionsanfälligkeit erhöht. Um das Risiko von Erkrankungen auf das unvermeidbare Minimum zu reduzieren, sind auf Basis einer sensiblen Erfassung von ersten Krankheitsanzeichen bzw. prädisponierenden Situationen weitere Maßnahmen sinnvoll. Futtermittelzusatzstoffe können zur Stärkung von Kälbern und damit Förderung ihrer Gesundheit eingesetzt werden. Insbesondere phytogene Zusatzstoffe haben in gut geführten Betrieben das Potential, die Notwendigkeit für antibiotische Behandlungen weiter zu reduzieren. Durch die Reduzierung der Häufigkeit von Erkrankungen in der Kälberaufzucht sowie damit verbunden eine Steigerung der Tiergesundheit und des Tierwohls, kann das Projekt einen substantiellen Beitrag zur Förderung der nachhaltigen Leistungsfähigkeit der Agrarwirtschaft bei bestmöglicher Förderung des Tierschutzes in der Landwirtschaft leisten.

Cooperation Partners:

Phytobiotics Futterzusatzstoffe GmbH

Funding: Deutsche Forschungsgemeinschaft (DFG) , 404.650 EUR

Project Details:
The genus Pestivirus belongs to the virus family Flaviviridae and comprises RNA viruses of great relevance, like Bovine viral diarrhea virus (BVDV) and Classical swine fever virus (CSFV), which are causative pathogens of notifiable diseases. Since decades, it was commonly accepted that pestivirus infections are restricted to cloven hooved (ungulate) hosts. In the past years, several atypical pestiviruses have been discovered in non-ungulate hosts. These newly discovered pestiviruses show the typical genome organization, but are genetically highly distinct. Obviously, these novel viruses represent a new group within the pestiviruses with so far uncharacterized biological properties. In addition, such a novel pestivirus was also discovered in pigs and designated "atypical porcine pestivirus" (APPV). APPV causes a neurological disease in newborn piglets (congenital tremor) and involvement in other diseases (e.g. infertility, abortion, neonatal malformations) appears likely.
Within this research project, it was possible to adapt APPV to cell culture conditions and to propagate it. The availability of a virus isolate provided the basis for further studies to characterize the biological properties of the pathogen. Our work demonstrated that there are obviously significant differences in the cell entry of APPV and CSFV. It has been believed for long time that the complement-regulating protein CD46 is the key for pestiviruses to penetrate the host cell, but our work showed that some pestiviruses - including CSFV - use a CD46-independent mechanism for cell entry. Which cellular surface structures are used instead for cell entry is still unclear and will be the subject of further research.
The aim of the study is to provide insights into the complex, probably multi-step process of cell entry. Within this project is the aim to identify the molecular determinants of cell entry of pestiviruses and to characterize them in more detail. Several host cell factors have already been identified which apparently interact with the viral envelope proteins during early phases of viral replication and can influence virus replication. First, it has to be elucidated whether these factors directly interact with the virus particles or whether these are indirect effects, e.g. caused by binding to other cellular proteins or by an altered cell metabolism. Knowledge of the key factors for the entry of porcine pestiviruses into the host cell can make a valuable contribution to understanding the biology of the new and widespread pathogen in the pig population, APPV, as well as the properties of the long-known animal disease pathogen CSFV.

Results:

https://www.tandfonline.com/doi/full/10.1080/22221751.2024.2327385

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