Research

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

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: Bundesanstalt für Landwirtschaft und Ernährung (BLE), 134.128 EUR

Project Details:
The overall goal of the project is that farms that have high antibiotic use (ABU) can learn from farms that have comparably low ABU and the identification and optimization of parameters to improve animal health. The specific objectives of the project are: to improve biosecurity and overall hygiene of broiler chicken farms, to improve animal health of broiler chickens, to minimize the use of antibiotics, to transfer knowledge between broiler chicken farms with low and high ABU, and to optimize risk areas based on knowledge transfer.
There should be an intensive exchange of experiences between farmers who have different levels of ABU within the project. Thus, farms that have a high need for antibiotic use at the beginning of the project will learn which parameters they can and should optimize to improve animal health and minimize antibiotic use. Farm management factors that have a potential impact on animal health and consequent necessary ABU will be evaluated and collected during the practical phases of the project. These factors are divided into respective work packages (WP), including biosecurity of the farm and hygiene management (worked on by FLI & UROS), cleaning and disinfection (UROS), animal health and stable or herd management (TiHo and LMU), and knowledge transfer (UROS).
The project thus involves farms that have already been able to minimize their antibiotic use through innovative measures, optimized management and improved husbandry conditions. In addition, farms that are interested in improving animal health and minimizing antibiotic use and want to learn from other farms are invited to participate.

Cooperation Partners:

Uni ROS; Prof. Helen Louton

LMU München; PD Dr. Elke Rauch

FLI Insel Riems; PD Dr. Nicolai Denzin

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: Drittmittelprojekt, gefördert durch die Deutsche Forschungsgemeinschaft (DFG)., 269.600 EUR

Project Details:
Bacillus cereus is a common soil bacterium responsible for two types of foodborne gastrointestinal diseases. The emetic variant leads to food poisoning and manifests in nausea and vomiting, while infections with enteropathogenic strains cause diarrhoea and abdominal pain. These symptoms are caused by various toxins, including the cyclic dodecadepsipeptide cereulide and the protein-based enterotoxins haemolysin BL (Hbl), non-haemolytic enterotoxin (Nhe) and cytotoxin K (CytK).
The principle of action of the pore-forming three-component toxin Hbl was investigated in detail in a previous project. The complex formation of the three protein components in solution, the binding order to the target cells, the optimum concentration ratio for fastest pore formation and maximum cytotoxicity, as well as the effect of a fourth protein component were determined. While the preliminary work focused on the toxin itself, this project investigates the effects of pore formation on the host.
This project provides answers to the cellular response of the primary target of B. cereus enterotoxins, namely human cells of the gastrointestinal tract. Firstly, relevant toxin concentrations and exposure times for the survival of intestinal cells or the onset of apoptosis will be determined. In addition, the onset of possible repair mechanisms within the target cells is investigated. These initial data already provide a model for the onset of diarrhoea caused by enteropathogenic B. cereus. Following these studies, the interaction of B. cereus and its enterotoxins with more complex structures, namely human intestinal organoids, is investigated. The use of organoid culture systems enables more elaborate studies on host-microorganism interactions. Various aspects are investigated, including gene expression, ion transport and the activation of signalling pathways within the target cells and structures.
Important new insights into the physiological processes that lead to enterotoxin-induced diarrhoea are expected.

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: MWK, 540.878 EUR

Project Details:
Comprehensive characterization of the hormone profiles of the HPG axis in male and female Long COVID patients, hormone panels, hormone measurements and statistical evaluations.
Creation of expression profiles of sex hormones and
sex hormone receptors in the plasma, lungs, reproductive organs and brains of male and female hamsters.

Results:

https://www.umg.eu/forschung/corona/cofoni/

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

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)