Overview of research projects

Funding: MELUND, 56.077 EUR

Project Details:
Research on marine mammals started in Büsum after the first seal mortality in 1988/89. The aim of the scientists is to study the biology and ecology of marine mammals and to assess the impact of humans on the animals, their health and their population. The scientific focus is on studies of health (exposure to pollutants, underwater noise, stress, immune system, infectious diseases, etc.) as well as behaviour, habitat use, population densities and impacts of anthropogenic interventions. Among other lines of research, the scientists are currently investigating the effects of underwater noise (e.g. from explosions, offshore wind turbines, shipping) on the behaviour and health of seals and harbour porpoises, chemical pollution and waste, disturbances and fishing on marine mammals. The stranding network ensures that whales and seals found on the coasts of Schleswig-Holstein can be reported, recovered and necropsied. The state of health is determined by means of further histological, microbiological and parasitological examinations. In this project, the tissues of porpoises found dead in the North Sea and the Baltic Sea will be examined for specific pollutants and the auditory apparatus will be analysed.
The following pollutants will be investigated in the liver and fat of harbour porpoises from waters in Schleswig-Holstein: polychlorinated biphenyls (PCBs) and derivatives, dichloro-diphenyl-trichloroethane (DDT), polybrominated diphenyl ethers (PBDEs) and mercury (Hg). The results of the toxicological investigation will be combined with the data on health status from the autopsies and an ecotoxicological assessment will be made. The results will be used for the development of further investigations for the various agreements, such as HELCOM, OSPAR, MSRL, and development of indicators.
For investigations of the auditory apparatus, dead harbour porpoises recovered within the framework of the small cetacean monitoring programme of the Land of Schleswig-Holstein should be collected immediately after reporting in order to remove and preserve the ears as fresh as possible for the investigation. In particular, harbour porpoises found dead after blasting and other impulse sound events as well as by-catches and live strandings shall be included. High-resolution computed tomography scans of the ear bones will be performed as well as confocal microscopic and histological examinations.
The studies on the auditory apparatus of harbour porpoises carried out in this project will be considered in the context of ongoing or completed studies at ITAW with similar questions. The results of this project will be used to assess whether changes in various structures of the auditory pathways may have been caused by exposure of harbour porpoises to explosions or other impulsive sound events.

Results:

Bericht an das Ministerium für Energiewende, Klimaschutz, Umwelt und Natur des Landes Schleswig-Holstein

https://www.schleswig-holstein.de/DE/fachinhalte/A/artenschutz/Downloads/untersuchungSchweinswale2021.pdf?__blob=publicationFile&v=1

Funding: MWK über UMG Göttingen, 44.446 EUR

Project Details:
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus Type 2) is the causative agent of COVID-19. The course of the COVID-19 pandemic so far has emphatically shown that a coordinated bundling of interdisciplinary and complementary expertise is necessary in order to decode the diverse aspects of the biology, pathology and epidemiology of SARS-CoV-2 and to use the knowledge gained clinically for the treatment of patients as well as for modeling the course of infection in the population. In order to be able to provide and implement such a holistic approach, the federal state of Lower Saxony offers ideal conditions with its internationally renowned science locations. We are therefore applying for financial support for collaborative research to set up a COVID-19 research network in the state of Lower Saxony (COFONI).

Funding: MWK über UMG Göttingen, 41.000 EUR

Project Details:
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus Type 2) is the causative agent of COVID-19. The course of the COVID-19 pandemic so far has emphatically shown that a coordinated bundling of interdisciplinary and complementary expertise is necessary in order to decode the diverse aspects of the biology, pathology and epidemiology of SARS-CoV-2 and to use the knowledge gained clinically for the treatment of patients as well as for modeling the course of infection in the population. In order to be able to provide and implement such a holistic approach, the federal state of Lower Saxony offers ideal conditions with its internationally renowned science locations. We are therefore applying for financial support for collaborative research to set up a COVID-19 research network in the state of Lower Saxony (COFONI).

Funding: MWK über UMG Göttingen, 34.750 EUR

Project Details:
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus Type 2) is the causative agent of COVID-19. The course of the COVID-19 pandemic so far has emphatically shown that a coordinated bundling of interdisciplinary and complementary expertise is necessary in order to decode the diverse aspects of the biology, pathology and epidemiology of SARS-CoV-2 and to use the knowledge gained clinically for the treatment of patients as well as for modeling the course of infection in the population. In order to be able to provide and implement such a holistic approach, the federal state of Lower Saxony offers ideal conditions with its internationally renowned science locations. We are therefore applying for financial support for collaborative research to set up a COVID-19 research network in the state of Lower Saxony (COFONI).

Funding: MWK über UMG Göttingen, 29.847 EUR

Project Details:
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus Type 2) is the causative agent of COVID-19. The course of the COVID-19 pandemic so far has emphatically shown that a coordinated bundling of interdisciplinary and complementary expertise is necessary in order to decode the diverse aspects of the biology, pathology and epidemiology of SARS-CoV-2 and to use the knowledge gained clinically for the treatment of patients as well as for modeling the course of infection in the population. In order to be able to provide and implement such a holistic approach, the federal state of Lower Saxony offers ideal conditions with its internationally renowned science locations. We are therefore applying for financial support for collaborative research to set up a COVID-19 research network in the state of Lower Saxony (COFONI).

Funding: SprinD GmbH, 263.866 EUR

Project Details:
The viral genome of an RNA virus is released into the cell, where the viral genome is amplified and its transcripts translated into proteins to form more copies the virus. CRISPR/Cas13 enzymes cleave different sites of the viral genome and its transcripts through a combination of crRNAs. Proliferation of the virus is blocked and transcripts to be translated into viral proteins are reduced.

Cooperation Partners:

Universitätsmedizin Göttingen (UMG), Prof. Elisabeth Zeisberg

Funding: Leibniz-Informationszentrum, Technik und Naturwissenschaften, Technische Universitätsbibliothek (TIB), Hannover, 3.560 EUR

Project Details:
In order to enable the students to think outside the box, the already existing offer at the TiHo is to
Instructional/learning videos are expanded. Film sequences are planned that contain basic information on the aquatic and terrestrial animal species researched at ITAW, with learning units on their anatomical and physiological aspects
Particularities. Film sequences on autopsies of the respective animal species are intended to further deepen the learning content and illustrate the fields of activity of the veterinarians at the ITAW. The approach is interdisciplinary
and can offer veterinary medicine and biology students as well as other interested parties insights into anatomical, physiological and pathological contexts. The basics are available and can be processed by a technically experienced assistant into an online module lasting about 90 minutes.

Funding: Deutsche Forschungsgemeinschaft (DFG), Bonn plus ein Doktorandenstipendium (HGNI, 1 Jahr, je 1300 ?), 75.850 EUR

Project Details:
CoVid-19 is characterized by infection of the airways by SARS-CoV-2. Apart from the respiratory tract, other organs are also involved, e.g. the intestinal tract. The importance of the intestinal infection is increasingly recognized. In a large proportion of pediatric patients, virus was detected in rectal swabs and virus shedding from the intestine was found even when oral swabs had become negative. Therefore, prolonged virus shedding and fecal-oral transmission have to be considered. This notion is supported by detection of the virus in wastewater.
The aim of this short project is to apply intestinal cell cultures to characterize the infection of differentiated intestinal epithelial cells by SARS-CoV-2 and thereafter intestinal orgranoids.
This in vitro infection approach will target the following aims:
1. Characterization of the replication efficiency of SARS-CoV-2 (virus yield, virus exit, virus entry, apical, basolateral).
2. Localization of the cellular receptor(s) in human intestinal Caco-2 cells
3. Investigation of the trafficking of the cellular receptor(s), determination and subsequent modulation of their mode of interaction with membrane microdomains (lipid rafts, LRs)
4. Effects of glycosylation modulators on the spike glycoprotein and its interaction with intestinal cells
5. Implication of virus infection on the trafficking and function of crucial enzymes of the intestinal physiology (APN, SI, LPH, DPP4).
This project will provide substantial information on the replication of SARS-CoV-2 in intestinal epithelial cells, evaluate its effects on the intestinal function and provide solid hypotheses on the molecular and biochemical basis for the symptoms elicited by SARS-CoV-2 infections. These hypotheses can be then examined at a later stage in intestinal organoids. Further, unravelling the biosynthetic pathway, glycosylation pattern and mode of interaction of the SARS-CoV-2 receptors and its modulation could constitute exquisite targets for potential therapy.

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: SprinD, 684.523 EUR

Project Details:
Current antiviral agents mainly target stages in the viral life cycle such as viral attachment to host cell or replication of viral RNA and DNA. Most of the available antiviral agents are effective against replicating viruses only, and due to the lack of specificity, many have adverse side effects. Particularly in endemic and pandemic disease outbreaks, there is additional challenge through virus mutagenesis and the development of viral variants. Therefore, approaches, which target various virus variants are urgently needed. Current paradigms in antiviral treatment involve usage of small molecules and/or therapeutic antibodies. Small molecules often have secondary targets and thus can cause side effects. Antibodies are expensive, their administration is mostly limited to clinical settings, and also they are affected by mutations. In an endemic or pandemic situation, therapies which have broad coverage within virus families, prevent transmission, and can be safely applied during mild and moderate illness are especially valuable.

Our novel approach aims to fill this need through the use of CRISPR/Cas13, an enzyme from bacteria, which cleaves RNA, including the viral genome (of RNA viruses) and of viral mRNA, thereby blocking viral replication and generation of viral proteins. Our therapeutic strategy has no secondary targets, and can be produced at GMP level at low cost. Through a specific combination of so-called crRNAs, Cas13 is directed to different viral mRNAs and to different sites within the viral genome. The crRNAs are selected such that no human RNA is targeted, and therefore no adverse side effects can be expected. This technology can easily be adapted for any single stranded RNA virus. Through targeting different and highly conserved regions, this approach antagonizes also emerging variants of the original virus.

Cooperation Partners:

Prof. Dr. Elisabeth Zeisberg, Universitätsmedizin Göttingen