Research

Project Details:
Microvillus inclusion disease (MVID) is a rare congenital disorder that is characterized by a villus atrophy and the presence of microvillus inclusion bodies (MVIBs). In experimental settings using cationized ferritin in human biopsies we have previously demonstrated that the inclusion bodies originate from autophagocytosis of apical cell membrane and represent early endosomes. The genetic defect in MVID has been meanwhile mapped to the MYO5B gene that encodes the unconventional type myosin 5b motor protein. Myosin 5b is associated with the plasma membrane recycling system in non-polarized cells and the apical recycling system in polarized cells. Furthermore, it has been shown that the Rab11 family interacting protein 2 associates with myosin 5b in regulating plasma membrane recycling. These findings underline the importance of unravelling the cellular mechanisms of autophagocytosis of the apical membrane of enterocytes in MVID membranes with the ultimate goal of designing appropriate therapeutic measures in this context. In this proposal we will generate intestinal Caco-2 cells in which myosin 5b has been downregulated, depleted or modified and assess at the molecular and biochemical levels the consequences on the trafficking and targeting of a panel of brush border membrane proteins. We will further investigate the function of inhibitors of protein transport and polarized sorting as well as vesicular trafficking in myosin 5b-depleted Caco-2 cells as potentiators of brush border membrane rescue. The data gained from the cell culture model will be confirmed and expanded into intestinal organoids that will be generated from intestinal biopsy specimens of MVID patients. In this model we will address similar questions to those in the cellular model and identify targets for (i) preventing the formation of MVIBs and (ii) potential restoration of proper trafficking and sorting of intestinal protein markers and reducing carbohydrate malabsorption. The ultimate goal is to test inhibitors and modulators of these targets that are the least toxic for enterocytes. These substances would then represent suitable candidates for clinical trials in MVID patients. Substances like vincristine (cytostatic drugs) and chlorpromazine (neuroleptic drugs) are already approved drugs for treatment in children, yet not for the use in MVID.

Project Details:
Das Ziel der Untersuchungen soll darin bestehen, Bakteriophagen pferdetypischer Krankheitserreger aus Genitalsekreten von Hengst und Stute zu isolieren und zu charakterisieren. Weiterhin soll die antibakterielle Wirksamkeit der isolierten Bakteriophagen im in vitro-Modell überprüft werden.

Funding: BMBF, 144.575 EUR

Project Details:
Das West Nile Virus (WNV) ist eine in allen Regionen der Welt verbreitete Zoonose und wird durch verschiedene Stechmückenarten auf wild lebende Vögel übertragen. Es kann sich aber auch auf Menschen und Pferde ausweiten, wobei es neben meist asymptomatisch Verläufen bei etwa 20 - 30 % der Erkrankten zu grippeähnlichen Symptomen ("West-Nil-Fieber") und in 1-2 % der Fällen sogar zur Ausbildung einer schweren, neuroinvasiven Form mit meist fatalem Ausgang kommt.
Im Jahr 2018 konnte das West Nil Virus in Deutschland neben Pferden und Vögeln auch erstmalig beim Menschen diagnostiziert werden und wurde 2019 bei 5 Personen als Krankheitsursache bestätigt. Im Gegensatz zur Anwendung im Pferde gibt es noch keine für den Menschen zugelassene Impfung, weshalb jene Entwicklung von großer Bedeutung ist. Hierfür sollen vergleichende Charakterisierungen der Immunantworten nach WNV-Impfung und WNV-Infektion bei Pferden ein besseres Verständnis liefern. Dazu gehört die qualitative Charakterisierung der WNV spezifischen Antikörperantworten sowie der Aktivierung von T Zellen. Darüber hinaus sollen mögliche Impfversager identifiziert, wie auch Kreuzreaktionen mit anderen Flaviviren, wie beispielsweise FSME, besser verstanden werden um somit die Entwicklung von WNV-Impfstoffkandidaten zur Anwendung im Menschen zu optimieren.
Ziel ist es eine verbesserte Bewertung der Wirksamkeit von einer WNV-Impfung beim Pferd zu finden und die WNV Pathogenese bei Tier und Mensch besser zu verstehen, damit neue therapeutische und präventive Strategien entwickelt werden können.

Funding: DFG, 240.125 EUR

Project Details:
Neurons in the intermedial nucleus of the lateral lemniscus (INLL) are implicated in cross-frequency integration of auditory signals in bats. Contrary to other auditory brainstem nuclei in rodents, INLL neurons show a strong biophysical heterogeneity, as membrane time constants range over three orders of magnitude. Correlated with the membrane time constant the neuronal output type shows onset, adapting and sustained firing behaviours. We intend to understand this cellular heterogeneity on the molecular, biophysical and synaptic level. Therefore, we combine functional characterisations of INLL neurons with their single cell transcriptome analysis. This project generates the cellular fundament of exploring the functional features of INLL neurons that is so far enigmatic.

Results:

Wicke KD, Oppe L, Geese C, Sternberg AK, Felmy F.: Neuronal morphology and synaptic input patterns of neurons in the intermediate nucleus of the lateral lemniscus of gerbils. Sci Rep. 2023 Aug 30;13(1):14182. doi: 10.1038/s41598-023-41180-8.

Funding: A128512 MWK Niedersachsen, Volkswagen Stiftung, 1.190.125 EUR

Project Details:
In this study we will collect and analyze more than 108 datapoints (proteomics, genomics, clinical and environmental data) from retrospective and prospective patient cohorts. For the first time, this study
will take into account the recent discovery of the tight association of human norovirus with host cell membranes and proteins and link it to clinical, environmental and ecological niche (microbiota) data.
The translational potential of PRESENt ranges from prognostic and preventive to therapeutic strategies for stratified patient groups. First, we aim to define prognostic biomarkers of severe and chronic gastroenteritis to stratify patient groups. Second, we will investigate how efficient
disinfectants can inactivate patient-derived membrane cloaked norovirus. Third, the microbiome signatures may inform about possibilities of microbiota therapies to alleviate the course of disease in critical patient groups. Finally, the informatics meta-analysis of the retrospective and prospective study will reveal in addition to prognostic biomarkers and microbiome signatures environmental and individual factors, which associate with severe gastroenteritis. In the future, this work will thus pave the way towards better prevention (biomarkers, environmental
factors, individualized disinfectant use) and care (targeting/modifying microbiome or host factors) of severe and chronic viral gastroenteritis.

Results:

https://www.translationsallianz.de/train-platforms/train-projects/present/?L=1

Cooperation Partners:

Prof. Dr. Wolfgang Neijdl, Leibnitz University

Prof. Dr. Michael Marschollek, Hannover Medical School

Dr. Benjamin Heidrich, Hannover Medical School

Dr. Till Strowig, Helmholtz Centre for Infection Research

Prof. Dr. Lothar Jänsch, Helmholtz Centre for Infection Research

Prof. Dr. Thomas F. Schulz, Medizinische Hochschule Hannover

Prof. Dr. Lennart Svensson, Linköping Universität, Schweden

Funding: MWK, 2.903.582 EUR

Project Details:
Development and testing of preventive and therapeutic measures against SARS-CoV-2 using experimental animal models such as ferrets, rabbits, hamsters and primates.

Funding: Deutscher Jugendverband e.V., 10155 Berlin, 19.720 EUR

Project Details:
Suitability of live traps for the development of intelligent trapping systems.

Funding: MWK, 11.851.000 EUR

Project Details:
Carrying out an animal experiment to test monoclonal antibodies in the established hamster model at the RIZ, including applying for animal experiments, carrying out the animal experiment, virus titration and analyzes to determine the viral load in the organs, PCR analysis, histopathological examination (assay scope of 2 organs per animal).

Funding: EU: ERASMUS+ Programm, 47.000 EUR

Project Details:
With the project VetRepos a Veterinary item Repository - an itembank for linear and adaptive progress testing will be developed. The project aims are among others:
1) Creating a test item databank containing psychometrically validated test items covering the veterinary subject areas and aligned with the required EAEVE "Day One Competences"
2) Establishment of a quality assurance system for assessment and approval of test items submitted to the databank
3) Establisment of linear and adaptive online progress test system

Results:

SCHAPER E, VAN HAEFTEN T, WANDALL J, IIVANAINEN A, PENELL J, MCLEAN PRESS C, LEKEUX P, HOLM P (2023): Development of a shared item repository for progress testing in veterinary education. Front. Vet. Sci. 10:1296514. doi: 10.3389/fvets.2023.1296514

https://www.vetrepos.eu/

Cooperation Partners:

University of Copenhagen (UCPH)

Utrecht University (UU)

University of Helsinki (UH)

Norwegian University of Life Sciences (NMBU)

Swedish University of Agricultural Sciences (SLU)

The European Association of Establishments for Veterinary Education (EAEVE)

Project Details:
The risk assessment tool for African swine fever (ASF traffic light)developed by the Verbund Transformationsforschung agrar Niedersachsen, University of Vechta, which is so far established in Germany and Switzerland, will be translated into Polish and applied on pig farms in Poland. The scores obtained are compared with those of German farms of the same size. Regional differences in biosecurity on pig farms are identified.

Cooperation Partners:

Barbara Grabkowsky, Verbund Transformationsforschung agrar Niedersachsen, Universität Vechta