Research

Funding: MWK, 22.000 EUR

Project Details:
The importance of the highly conserved protein Nsp15 for the infection of cells by coronaviruses has been studied in detail in recent years. As an endonuclease, it rapidly recognizes and degrades both single-stranded (ssRNA) and double-stranded RNA (dsRNA). In addition, evidence from animal models suggests immunomodulatory properties of Nsp15 during early viral infection, leading to a delayed immune response. This process is ultimately involved in the development of acute respiratory failure, which is the main cause of COVID-19 mortality. As part of this funding program, we plan to develop new inhibitors of this protein through structure-guided design. Promising compounds will be characterized with respect to their ADME and physicochemical properties in order to obtain orally bioavailable compounds for the treatment of future viral pandemics.

Results:

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

Funding: MWK, 220.890 EUR

Project Details:
CRISPR/Cas13-mediated antiviral therapy against SARS-CoV-2 and its variants: a novel technology to target viral genome

Results:

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

Funding: Frauenhofer ITEM, 278.466 EUR

Project Details:
Frauenhofer ITEM-Therapeutic treatment against SARS-CoV-2 with inhaled VHH from BiondVax - Efficacy program in hamsters

Funding: DFG, 110.700 EUR

Project Details:
Tetraspanins are evolutionary conserved integral membrane proteins of 200-350 amino acid lengths. Through their large extracellular loop they mediate protein - protein and protein - lipid interactions in cellular membranes thereby shaping membrane microdomains called ?tetraspanin webs?. In humans and mice 33 tetraspanins are described and mosquito species express at least 15 tetraspanin orthologs. In mammalian cells, tetraspanins are host co-factors for several viruses including papillomaviruses, influenza virus, hepatitis C virus, HIV-1 and coronaviruses (Gerold et al., 2015; Bruening et al. 2018; Banse et al., 2018; Alberione et al. 2020; Palor et al., 2020). For hepatitis C virus, colleagues and we showed that the tetraspanin CD81 is a host range determining factor (Vogt et al. 2013; Scull et al., 2015; von Schaewen et al., 2016).
The proposed project aims at characterizing in detail, which of the 33 human tetraspanins in addition to CD81 are host factors for alphaviruses and whether tetraspanins from reservoir species, dead end host species and transmitting mosquito vectors serve as host factors of alphaviruses. Thereby the work will contribute to the understanding of the molecular composition and function of alphavirus replication complexes and determine the role of tetraspanins in species range, transmission and consequently emergence of alphaviruses.

Funding: Verein für Bioökonomieforschung (FBF), 9.600 EUR

Project Details:
The FBF funded project "Influence of stress during rearing management and later eligibility in sperm production" revealed a clear difference in a developed management score and in mean testosterone concentrations between young bulls with good versus poor sperm quality. However, due to a lack of sensitivity, hormone measurements could not be used as adequate diagnostic tests to identify very good or bad bulls with regard to their later performance and performance persistence, neither at an age of four months nor later at the first semen collection.
This more in-depth study is designed to search for better biomarkers using proteomics as non-target approach. Bulls with a very good versus bad performance persistence over two years will be analyzed by mass spectrometry using the plasma samples collected close to the first semen collection during the preliminary project. Data sets of the mass spectrometric measurements with identified peptides will be matched with a bovine protein database to finally name proteins of the plasma samples. Both groups of bulls will be compared with respect to the proteins identified and the amounts of the same.
In order to establish test methods that are as practicable as possible, promising fertility-associated proteins will subsequently be measured in the blood samples from all age classes investigated during bull calf rearing using commercially available ELISA kits. These data will be used to establish reference ranges and thresholds using receiver operating characteristic (ROC) analyses. Optimally, suitable biomarkers in the blood allow an early preselection of bull calves that are eligible for the collection of quantitatively and qualitatively good semen.

Cooperation Partners:

Institut für Toxikologie, Medizinische Hochschule Hannover

Funding: Niedersächsischen Ministerium für Wissenschaft und Kultur , 50.000 EUR

Project Details:
Veterinarians and their employees have a relatively high risk of accidents at work, whether in the clinic, in the diagnostic laboratory or in research. Occupational accident and illness risks in the workplace can be reduced through systematic prevention. Only those who know the specific risks and exposures can minimize them. Safety and health during studies, and later at work in the long term, are the areas that everything should revolve around here. Experience has shown that occupational safety and infection prevention are not the most popular topics and are often only considered relevant once a risk factor has been acutely identified or an accident has already occurred.
The aim of this project is to generate a game-based and collaborative course that uses interactive and digital elements as well as a workshop-based face-to-face event to convey the topic of active occupational safety using memorable practical examples and thus accompany the participants throughout their studies. The aim is to create a profound understanding with long-lasting learning success.

Funding: QS-Wissenschaftsfonds, 28.229 EUR

Project Details:
The core of the research project is to answer important questions regarding the spatiotemporal impact of restrictions due to the Covid 19 pandemic on the value chain of poultry meat production. Data from primary production, structural analyses as well as data on slaughter findings, reported zoonoses in the German population and restrictions due to the pandemic will be linked to derive significances and correlations. From this, important propositions are generated, which address and evaluate the resilience to massive interventions of the integrated process chains in global world trade.

In particular, the project will demonstrate whether the reduction in reported Campylobacter enteritis in the population during the pandemic was due to changes in the occurrence of the pathogen in primary production, process flows in slaughterhouses, changes in consumer behavior, or other factors. The restrictions of the Covid 19 pandemic are included in the synthesis of the results.

Funding: TU München, 158.232 EUR

Project Details:
We hypothesize that the stabilization of the vascular system by low-dose ligands to activate the integrin αvβ3 should have beneficial effects on COVID-19 infected patients. We here investigate the effects of the synthetic ligand cylengitide and 29P for integrin αvβ3 in an animal model of SARS-CoV-2 infected hamsters in which the destruction of the vascular system in association with formation of neutrophil extracellular traps has previously been documented.

Funding: DFG, 117.450 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. Ältere Individuen haben ein höheres Risiko, eine solche neuroinvasive Form zu entwickeln.
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. In Anbetracht des erhöhten Risikos einer schweren Erkrankung bei älteren Individuen ist insbesondere für diese Gruppe ein Impfstoff von hohem Interesse. Dies wird dadurch erschwert, dass Impfungen in dieser Gruppe zu einer schwächer ausgeprägten und damit weniger effektiven Immunantwort führen können. Daher soll die Immunantwort älterer Mäuse auf den von uns entwickelten Impfstoff gegen das West-Nil-Virus charakterisiert werden, insbesondere in Hinblick auf die Entwicklung einer T-Zell-Immunität.
Ziel ist es, die WNV Pathogenese bei Tier und Mensch und die Impfstoff-induzierte Immunantwort im Hinblick auf schützende Korrelate besser zu verstehen, damit neue therapeutische und präventive Strategien entwickelt werden können.

Funding: DZIF, BMBF, 65.000 EUR

Project Details:
In May 2022, an unprecedented multi-country outbreak of monkeypox affecting Europe, North America, the Middle East, and Australia was recognized. Monkeypox (MPX) is a re-emerging, zoonotic, and potentially life-threatening viral disease caused by monkeypox virus (MPXV), an orthopoxvirus endemic in Central and West Africa. As of June 28th 2022, a total of 4119 confirmed cases have been reported worldwide (ECDC), including 676 confirmed cases in Germany (RKI). This is the first time that chains of human-to-human MPXV transmission are documented without epidemiological links to West or Central Africa. At present, most cases are detected in young men, self-identifying as men who have sex with men, and associated with mild clinical symptoms. However, MPXV may cause severe disease in risk groups of the population (young children, pregnant women, immunosuppressed persons), and a spread of MPX into the general population is to be expected as most of the younger population (<50-60 years of age) lack virus specific immunity because of the end of smallpox vaccination programmes in the 1980ties. Thus there is a risk of an extended period of MPX circulating also outside of Africa, and ongoing efforts in the public health response must interrupt MPX transmission chains and clear MPXV from its new environment as soon as possible. Current countermeasures include the use of a licensed smallpox vaccine (IMVANEX) based on Modified Vaccinia virus Ankara (MVA) and a licensed drug against smallpox (Tecovirimat). STIKO recommends vaccination with IMVANEX as post-exposure prophylaxis for contacts of MPX patients and for persons at high risk of exposure.
The aim of this application is to support this counteraction measures against the MPX outbreak by preparing for the development and clinical use of the DZIF MVA-SARS-2-S candidate vector vaccine as bivalent vaccine against MPX and COVID-19 including the establishment of a preclinical model for immunogenicity and efficacy testing.

Cooperation Partners:

Prof. Dr. Marylyn Addo, UKE Hamburg

Prof. Dr. Gerd Sutter, LMU München