Research

Funding: This work was supported by COVID-19 Research Network of the State of Lower Saxony (COFONI) with funding from the Ministry of Science and Culture of Lower Saxony, Germany (14-76403-184) and by PRACTIS—Clinician Scientist Program of Hannover Medical School, funded by the German Research Foundation (DFG-ME3696/3-1)., 50.000 EUR

Project Details:
Vaccination is an important measure in controlling the COVID-19 pandemic. However, there were pharmocovigilance concerns as a very rare but potentially disastrous complication was identified after application with the ChAdOx1 nCoV-19 vaccine, i.e. cerebral sinus thrombosis, but also further thrombotic complications including ischemic stroke. Meanwhile, the most likely mechanism has been identified as platelet factor 4 (PF4) antibody mediated immune thrombotic thrombocytopenia, a mechanism which is already known from heparin-induced thrombocytopenia (HIT). Interestingly NETs were suggested to be critical for thrombus formation in the HIT-pathophysiology as well. Markers of NETosis were observed in platelet-rich thrombi in the lungs of mice with HIT. Therefore, NETs might also be involved in vaccine-induced immune thrombotic thrombocytopenia (VITT) mediated thrombotic complications and might therefore be a common trunk in the pathogenesis of COVID-19 and vaccine-induced complications. Moreover, biomarkers reflecting NETs burden in the circulation and within tissue specimens (e.g. cerebral thrombi) may be suitable as diagnostic, therapeutic or prognostic targets in thrombotic diseases. Most importantly, there is a tremendous need to identify patients at risk for cerebrovascular complications due to both COVID-19 and VITT. The proposed project ISI-VITT is intended to contribute to addressing this issue.

Cooperation Partners:

Cerebrovascular Research Group (Head: Prof. Dr. Karin Weissenborn), Deptartment of Neurology, Medical School Hannover: Dr. Ramona Schuppner & Dr. Gerrit M. Grosse

Prof. Dr. Christine Falk, Institute for Transplantation Immunology, Medical School Hannover

Funding: MWK Niedersachsen, 69.925 EUR

Project Details:
Since the first description of SARS-CoV2 and the related disease COVID-19 in December 2019 various in vitro and in vivo models were utilized to investigate viral life cycle and pathophysiology as basis for effective treatment strategies. In vivo models used to investigate SARS-CoV2 or respiratory viral infections in general range from small animals models to non-human primate models (Munoz-Fontela et al., 2020). But next to the ethical questions accompanying animal models in scientific research also not all questions related to human respiratory epithelium can be examined with (small) animal models. Immortalized human cell lines like Caco-2, Calu-3 or HEK293T which are regularly used to investigate respiratory viruses like influenza or Human Respiratory Syncytial virus (RSV) and also Corona Virus infections (SARS, MERS) are frequently applied to investigate infection and replication of SARS-CoV2; however, although these cell lines are comparatively easy and cost effective to grow, they only poorly recapitulate physiological conditions of the respiratory epithelium. Even cell lines such as A549 cells barely reflect the phenotype of lung epithelium. Human primary bronchial epithelial cells (hBECs) represent a more physiological in vitro model and are also utilized in SARS-CoV2 research (Hoffmann et al., 2020). These cells can be isolated from donor lung tissue, expanded in vitro and matured in Air-Liquid-Interface (ALI) cultures (Hoffmann et al., 2020). While the main focus of our group is scalable generation and utilization of cardiovascular and respiratory derivatives from induced pluripotent stem cells for disease modelling, drug screening and cellular therapies (Merkert et al., 2019; Katsirntaki et al., 2015; Kempf et al., 2014; Schmeckebier et al., 2013; Zweigert et al., 2011), we have recently also established isolation of primary human airway cells of consistent high quality: Hannover Medical School is the leading German lung transplantation center with about 100 lung transplantation per year. In close collaboration with our transplant surgeons and the group of Prof. Danny Jonigk (Pathology, MHH), we are routinely preparing hBECs from bronchial tissue that can be culture-expanded and cryopreserved for later applications. Also maturation of these hBECs is already well established in our group and matured proximal epithelial cells are already provided to partners for investigation of SARS-CoV2 as well as other respiratory viral infections (e.g. RSV). While these primary hBECs represent a superior in vitro model for SARS-CoV2 infection studies and COVID disease modelling, they do represent only one respiratory compartment. Infection by SARS-CoV2 not only occurs in the upper throat and nasal tract, trachea and bronchi, but also in the alveolar epithelium. Therefore also organotypic in vitro models that reflect the distal lung compartment are urgently required. While maintenance and expansion of isolated type II alveolar epithelial cells (AT2 cells) was so far impossible, substantial progress was very recently made, and protocols that enable production of such cells in larger numbers have been developed. So called Alveolospheres, organoids consisting of alveolar type 1 and 2 cells, allow expansion and maturation of isolated distal epithelial cell in vitro and were recently used to model SARS-CoV2 infection (Karsura et al., 2020; Salahudeen et al., 2020). Although organoid cultures enabled in vitro culture of AT1 and AT2 cells, we believe ALI cultures would represent a more physiological system with air exposure of the epithelial cells and could subsequently allow co-culture systems with endothelial cells as well as macrophages to create more complex organotypic in vitro models of the alveolar lung compartment. By utilizing our experience from differentiation of induced pluripotent stem cells (Katsirntaki et al., 2015; Schmeckebier et al., 2013) we aim to establish isolation, 2D expansion and cryopreservation of human AT2 cells, and further maturation and differentiation in type I alveolar epithelial (AT1) cells in an ALI culture system for in vitro modelling of SARS-CoV-2 infections.

Cooperation Partners:

Prof. Dr. Ulrich Martin, Dr. rer. nat. Ruth Olmer

Leibniz-Forschungslaboratorien für Biotechnologie und künstliche Organe, Klinik für Herz-, Thorax-, Transplantations- und Gefäßchirurgie - Medizinische Hochschule Hannover

Funding: COVID 19 Forschungsnetzwerk Niedersachsen COFONI, 48.638 EUR

Project Details:
Early detection of individuals with a SARS-CoV-2 infection remains the most important tool to interrupt the chain of infection. Several studies have already proven canines’ extraordinary olfactory acuity to detect SARS-CoV-2-infected individuals. However, with increasing knowledge about the virus, the variety and chronicity of the disease expression and an increase in the number of people that are vaccinated, some questions have not yet been answered. We will test a variety of hypotheses to further explore the use of detection dogs as a screening method for SARS-CoV-2-infections.

Results:

Dogs can distinguish SARS-CoV-2-infections from other viral infections. However, compared to earlier studies our scent dogs achieved lower diagnostic sensitivities. To deploy COVID-19 detection dogs as a reliable screening method it is therefore mandatory to include a variety of samples from different viral respiratory tract infections in dog training to ensure a successful discrimination process.

https://doi.org/10.3389/fmed.2021.749588

Cooperation Partners:

Medizinische Hochschule Hannover

Funding: Niedersächsische Ministerium für Wissenschaft und Kultur, 1.225.000 EUR

Project Details:
Auf das Coronavirus trainierte Spürhunde werden in diesem Herbst bei mehreren Musikveranstaltungen eingesetzt und mit Antigen- und rtRT-PCR-Tests verglichen. Dies wird weitere Erkenntnisse darüber liefern, wie Corona-Spürhunde am besten bei der Detektion infizierten Menschen eingesetzt werden können.

Results:

www.backtoculture.de

Cooperation Partners:

Medizinischen Hochschule Hannover,

Universitätsklinikum Hamburg-Eppendorf,

Hannover Concerts,

Proevent,

Awias Aviation Services

Funding: QS-Wissenschaftsfonds, 30.000 EUR

Project Details:
The aim of this study is to determine the sound level in pigs' nursery compartments and to detect the effects of animal behaviour and barn technology on the sound level.
In addition, occupational safety will be considered in the study by identifying particular sound events to which both, animals and humans are exposed, and quantifying them with regard to the sound pressure level. The aim is to generate representative data on noise pollution in today's piglet rearing in Germany, to determine the origin of noise pollution and - if necessary - to identify potential for improvement in terms of animal welfare and occupational safety.

Results:

https://doi.org/10.1016/j.livsci.2024.105410

Project Details:
Frequencies of Actinobacillus pleuropneumoniae isolates resistant against various antimicrobial substances will be compared in the years 2006-2021. Frequencies of coinfecting agents will be determined.

Results:

doi: 10.3389/fvets.2021.802570

Funding: Projektförderung aus dem Europäischen Landwirtschaftsfonds für die Entwicklung des ländlichen Raums (ANBest-ELER 2021, Europäischen Innovationspartnerschaft "Produktivität und Nachhaltigkeit in der Landwirtschaft" (EIP Agri), 89.794 EUR

Project Details:
Suboptimal availability and quality of drinking water as well as a lack of hygiene in water pipes on pig farms can cause animal welfare and health problems. Insufficient water intake due to technical deficiencies, low palatability due to e.g. biofilm formation in the pipes or a restrictive water supply represent a massive stressor for animals and can lead to health impairments that promote other diseases (e.g. ear and tail injuries, diarrhea).
In this project, a new drinking water pipe cleaning concept for piglet rearing farms will be established and tested for practical use in two rearing barns. The system, developed in a collaborative project and tested under laboratory conditions, will be used to clean water pipes contaminated with plaque, to destroy Salmonella reservoirs in the pipes, and to reduce endotoxin contamination. It is exspected, that ear and tail lesions will be reduced after cleaning the drinking water pipes in case that they are related to endotoxins. After technical, chemical and microbiological analyses, as well as examinations of the piglets, the drinking water pipe cleaning is carried out on the farms. A newly developed mobile flushing device and a new substance containing tartaric acid and catalytic additives are used. The substance is highly effective against biofilms and also destroys the genetic material of pathogens. The effects of this cleaning concept will be measured and evaluated on two farms in three baches respectively.

Cooperation Partners:

Landwirtschaftliche Betriebe

Aumann Hygienetechnik

ConVet GmbH&Co. KG

Funding: Herbonis Animal Health GmbH Rheinstrasse 30 4302 Augst BL, Schweiz, 4.300 EUR

Project Details:
Solanum glaucophyllum (waxy nightshade) is one of the few plants that naturally produces 1,25-dihydroxycholecalciferol glycosides (1,25(OH)2D3-gly). In the literature it is mentioned that the glycosides are cleaved before absorption and thus only the aglycone is absorbed. However, no data are known so far that confirm this assumption analytically. In a multi-stage approach, this question is to be clarified in vitro. To do this, a number of preliminary tests must first be carried out, including one focusing on possible cell toxicity. Since the cell toxicity of 1,25(OH)2D3-gly can only be extrapolated from the data for synthetic 1,25(OH)2D3 to a limited extent, this experiment serves to determine the maximum possible dose.

Cooperation Partners:

Herbonis Animal Health GmbH

Rheinstrasse 30

4302 Augst BL, Schweiz

Funding: EU, 8.320 EUR

Project Details:
The overall aim of the HELCOM BLUES project is to support regional capacity, coordination and cooperation with regards to developing effective measures to secure good status of the marine environment. This includes provisioning, and making available, necessary knowledge to advance the development and implementation of joint measures addressing common pressures, as well as to provide concrete support to the decision-making process within the Baltic Sea region.
The task carried out by TiHo focuses on highly mobile and under-reported groups (here: cetaceans), and considers several aspects identified in recent HELCOM review processes to be knowledge/assessment gaps and aspects of high regional priority. The harbour porpoise can be categorised as both a highly mobile and an under-reported species in the Baltic Sea region. At present, there are no functional regional HELCOM indicator(s) to assess status for abundance or distribution, which are two of the primary Marine Strategy Framework Directive criteria under MSFD D1. This clear gap was identified as a high priority for the HELCOM region. This task will provide support for the HELCOM indicator team and focus on improving methods and operational assessments of harbour porpoise abundance by HOLAS III, and on harmonising methods of assessment with other EU regions (i.e. OSPAR and HELCOM). The main aspects addressed by TiHo are:
1) Establishment of a harmonised approach to indicator development for harbour porpoises between HELCOM and OSPAR (of particular relevance to shared marine areas);
2) Assessing trend in abundance for assessment of the Belt Sea population;

Results:

final report of the EU project "HELCOM BLUES"

https://blues.helcom.fi/wp-content/uploads/2023/09/HELCOM-BLUES_Activity_2.4-Harbour-porpoise-Main-report.pdf

Cooperation Partners:

Project coordinator

Helsinki Commission (HELCOM), Finland

Partners

Kiel Institute for the World Economy (IfW), Germany

University of Hamburg, Germany

Natural Resources Institute Finland (LUKE), Finland

Finnish Environment Institute (SYKE), Finland

Swedish University of Agricultural Sciences, Department of Aquatic Resources (SLU Aqua), Sweden

Stockholm University (SU), Sweden

Swedish Meteorological and Hydrological Institute (SMHI), Sweden

Swedish Agency for Marine and Water Management (SwAM), Sweden

Tallinn University of Technology (TalTech), Estonia

University of Tartu (UT), Estonia

Center for Environmental Policy (AAPC), Lithuania

Latvian Institute of Aquatic Ecology, Latvia

Funding: ALZCHEM, 39.065 EUR

Project Details:
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