COFONI - COVID-19 Research Network Lower Saxony
The aim of the COFONI collaborative research project is to investigate fundamental and important questions about the virus, the molecular basis for the development of active agents and vaccines, and the prediction and influence of the pandemic over a longer period of time. New findings should help to develop new forms of therapy and provide the state of Lower Saxony with further tools to protect the population from infections with SARS-CoV-2.The cross-location networking in the COFONI research network is centrally coordinated by the University Medical Center Göttingen (UMG). Prof. Dr. Jürgen Wienands, Dean of Research at UMG, heads the central coordination office together with Prof. Dr. Maren von Köckritz-Blickwede from the University of Veterinary Medicine Hannover (TiHo). Research in the network is expected to begin in early 2021.The COFONI research network brings together the core scientific competencies available in the metropolitan regions of Göttingen, Hannover and Braunschweig in four key areas that are of crucial importance for the management of the Corona pandemic:
1. epidemiological modeling for pandemic response
2. antiviral strategies via agents and vaccines
3. digital infectious medicine for individualized patient care
4. pathophysiology for immune modulation and control
A central technology platform provides all network participants with interdisciplinary methods and animal models as well as data bases and biobanks for joint use with the greatest possible efficiency. All research institutions from Lower Saxony can apply for funding from the COFONI pot for project proposals in the four key areas. The respective local institutions of the Leibniz Association and the Max Planck Society can also participate in the future research projects. For the scientific quality assurance of the projects, external expert opinions are to be obtained for the applications from persons with specialist expertise.
DeCOI - German COVID-19 OMICS Initiative
In severe cases of COVID-19 disease, contrary to what has been generally assumed up to now, there is not only a strong immune reaction - the immune response is rather caught in a continuous loop of activation and inhibition. Experts of the Charité - Universitätsmedizin Berlin, the University of Bonn, the German Center for Neurodegenerative Diseases (DZNE), the Helmholtz Center for Infection Research (HZI) and the German Center for Infection Research (DZIF) present these findings together with colleagues of a nationwide research network in the scientific journal Cell.
Schulte-Schrepping et al.: Severe COVID-19 is marked by a dysregulated myeloid cell compartment. Cell (2020), DOI: 10.1016/j.cell.2020.08.001
- Charité - University Medicine Berlin
- German Center for Infection Research (DZIF)
- German Center for Neurodegenerative Diseases (DZNE)
- Helmholtz Institute for RNA-based Infection Research (HIRI)
- Helmholtz Centre for Infection Research (HZI)
- University of Bonn
- Center for Individualized Infection Medicine (CiiM)
Corona: Everything at a glance with the ORKG
Several new scientific articles on COVID-19 are published daily. Many publishers have decided to support COVID-19 research and publish articles related to the crisis topic as Open Access. Access to scientific articles is of crucial importance for research. The organization of the information published in them is essential, but extremely time-consuming. And under these circumstances, time is an asset that is more valuable than ever.
Prof. Dr. Sören Auer and his team in the Joint Lab of L3S and TIB want to use the Open Research Knowledge Graph (ORKG) to make the organization of scientific knowledge more efficient. The ORKG presents the knowledge published in scientific literature in a structured way, so that it can be processed by machines and is ultimately more easily available.
Generation of a SARS-CoV-2 susceptible mouse model
In order to develop a preclinical mouse model of SARS-CoV-2 infection together with the DPZ, animals will be mated that express the human ACE2 receptor as the virus entry receptor and in which the type I interferon system can be specifically switched off on pneumocytes of the lung. In the course of the infection, similar symptoms and diseases to those in humans should develop. In cooperation with the Cantonal Hospital in St. Gallen, Switzerland, researchers are using a coronavirus model in mice to investigate why many patients lose their sense of smell as a result of COVID-19 disease.
Establishment of animal models
Before new vaccines or active pharmaceutical ingredients can be tested on humans, the efficacy and safety of the new substances must be tested on animals in the so-called preclinical phase. For this purpose, suitable animal species have to be found and the experimental design has to be adapted to the respective questions. For studies on SARS-CoV-2, these could be ferrets, rabbits, hamsters or mice. The experimental design follows the highest possible animal welfare standards as well as the requirements of biosafety level 3 (BSL3).
Influence of oxygen deficiency on the immune system and resulting improvement of animal experiment substitution methods
In severe cases of COVID-19 infection, oxygen plays a decisive role in the survival of the patient. It is therefore necessary to study the immune system under reduced oxygen conditions in order to understand the basic mechanisms of the disease process. TiHo researchers have already established a technique that enables them to measure the oxygen levels in the infected tissue, i.e. where the immune cells are active, in animal experiments. The values obtained will finally be used to develop animal experiment substitution methods.
Study on neurological damage caused by COVID-19
N-RENNT is a research network for brain infections. Many neurological diseases are caused by infections. Viruses, bacteria or parasites can be the cause of diseases of the central nervous system (CNS) in humans as well as in animals or they can have a negative influence on the course of the disease. And there have also been reports of neurological damage in COVID-19, such as loss of the sense of taste. The network will investigate neurological damage caused by COVID-19.
- Helmholtz Centre for Infection Research (HZI)
- Max Planck Institute for Experimental Medicine Göttingen
- Hannover Medical School (MHH)
- University of Veterinary Medicine Hannover Foundation (TiHo)
- Technical University of Braunschweig
- TWINCORE - Centre for Experimental and Clinical Infection Research
- University Medicine Göttingen (UMG)
Alternative methods to animal testing
The research association "R2N - Replace and Reduce from Lower Saxony - Replacement and Supplementary Methods for Future-oriented Biomedical Research" is funded by the Lower Saxony Ministry of Science and Culture. The aim is to find methods that allow biomedical research in the field of lung infections in humans and animals and to avoid animal experiments. In a sub-project of the network, the TiHo is establishing a tissue and cell bank. For this purpose, the researchers collect and preserve samples with cells and tissue components from the respiratory system. The samples are thus available for projects at any time to research alternatives to animal experiments. The TiHo researchers now also use this tissue and cell bank for corona research.
PhD Program VIPER - Virus Detection, Pathogenesis and Intervention
The German Research Foundation has been funding the PhD program VIPER - Virus Detection, Pathogenesis and Intervention at the TiHo since 2019. The aim of VIPER is to train a new generation of virus researchers to get to the bottom of new and recurrent virus infections. For three years, 28 young virus researchers will work on their doctoral theses. Much of the knowledge gained from this work can be used for corona research. In addition, they take part in lectures and practical courses specifically tailored to virus research, during which they learn where different viruses occur, how they interact with human and animal cells and how they can be detected and combated. Different disciplines work together interactively in the research project.
ANI-CoV - Pets as potential vectors for the transmission of SARS-CoV-2
Sub-project B: in-vitro culture systems
The ANI-CoV project is investigating which domestic and farm animal species as well as exotic animal species are susceptible to SARS-CoV-2 and may possibly transmit this virus to humans or other animal species. The focus of the project is on pets and farm animals, as humans are in regular and close contact with these animals. Susceptibility will be investigated using primary cell cultures obtained from the upper and lower respiratory tract.
Furthermore, the influence of SARS-CoV-2 infection on morphological and functional changes in respiratory tissue will be investigated. In addition, cellular factors and/or viral adaptations required for viral entry into new host species will be identified.
Corona-Access: Establishment of a SARS-CoV-2 model for drug discovery and testing in S2 laboratories
Research on SARS-CoV-2 and efficacy testing of drug candidates against the virus is only possible in laboratories with safety level 3. S3 laboratories are not available in all research institutions and working under so-called S3 conditions is very challenging. The project will establish a coronavirus model that can also be used under the lower safety level 2. The model is based on non-infectious virus-like particles. Thesevirus-like particles are virus particles that do not contain nucleic acids, which means that they cannot be propagated in the target cells and are therefore also used for vaccination purposes. With the help of these virus-like particles, drug candidates can be tested in alternative in vitro and ex vivo models, such as human precision lung sections (PCLS), under S2 conditions. Such a SARS-CoV-2 model can also be used to investigate risk factors for more severe courses in vulnerable groups.
Filter4Flow: Intelligent virus filter for SARS-CoV-2 patients
Patients with a severe course of COVID-19 disease often need to be ventilated, non-invasively or in intensive care. In both cases, monitoring of respiratory function and respiratory parameters is required. The patients and also the medical staff should be protected from a virus infection if possible. An intelligent virus filter, which can be used for both non-invasive and invasive ventilation, should make this protection possible. In the Filter4Flow project, Fraunhofer scientists and cooperation partner companies Aircontrols and ELKare are developing such an intelligent virus filter - a novel combination of fast sensor elements for measuring respiratory flow, pressure and respiratory gas as well as a virus filter. The signals are digitized and transmitted quickly and wirelessly to a respiratory system or a patient monitoring device (e.g. app). The intelligent virus filter enables accurate, reliable and at the same time cost-effective monitoring of the breathing of a large number of patients while also providing a filter function to protect patients and staff against infection. This helps to prevent the feared shortage of ventilation stations.
Development of antiviral strategies against SARS-CoV-2 target proteins
In this project, coronavirus proteins are produced, which are particularly in focus as candidates for diagnostic purposes, therapeutic target proteins and as possible candidates for protein-based vaccines - as a vaccine against SARS-CoV-2, but also for the time after that. To identify active substances, suitable tests are developed and applied to the substance libraries available at the HZI (approx. 40,000 substances). Interactions of drugs and antibodies with coronavirus proteins are analysed by biophysical methods to determine affinities and inhibition constants. Furthermore, structural biological methods such as cryo-electron microscopy or X-ray structure analysis are used. The effect of the drug candidates will be validated in the assay with the intact virus.
Extension of the GenoSurf search engine to SARS-CoV-2 data
Since the outbreak of the corona crisis, more and more information on SARS-CoV-2 has been integrated into public bioinformatics databases. The database management group headed by Professor Stefano Ceri at the Politecnico di Milano aims to support biologists in interpreting the increasing information. Within the framework of the ERC Advanced Grant "Data-Driven Genomic Computing", the research team has developed the search engine GenoSurf, which will enable bioscientists to query freely accessible human sequencing data according to a variety of available criteria. In order to contribute to the understanding of the corona virus and its spread, the group is extending GenoSurf to include viral genomes and starting with freely accessible information on SARS-CoV-2. The L3S research center is involved in the integration of genome modifications into the search engine and supports learning approaches for data that enable the machine generation of biological hypotheses.
Specialized Information Service Pharmacy
With the PubPharm research platform, the Specialized Information Service (FID) Pharmacy at the TU Braunschweig offers comprehensive and service-oriented access to pharmaceutical information resources. On the one hand, the FID thus makes a significant contribution to the full text supply of the subject by licensing journals of special demand, which are accessible campus-wide at the university locations of the subject. On the other hand, the central services of the FID offer unique selling points that are in demand compared to other platforms, such as innovative research tools focused on active ingredients and drugs. Thus, a semantically enriched search based on machine-learning technologies enables the display of related substances, diseases/symptoms and genes when searching for drugs and diseases/symptoms. At the same time, freely accessible subject-specific information resources (including DrugBank, BRENDA, PubChem, ChEMBL, etc.) are integrated to provide further drug-related data.
The current coronavirus pandemic shows that bio-medical research platforms have to adapt flexibly and quickly to new information needs in order to provide scientists with up-to-date information. The context-based services of the FID were therefore updated with regard to COVID-19 and SARS-COV-2 and integrated into PubPharm. The FID is also participating in the Open Research Challenge on COVID19 (see CORD-19 Research Challenge of the Allen Institute for AI). The corresponding approx. 50,000 full-text publications were annotated with a specially developed tagging pipeline. These annotations were then made available to the community. The corresponding services are, of course, continuously expanded as new literature is published.
The close cooperation between the University Library Braunschweig (UB) and the Institute for Information Systems (IfIS) of the TU Braunschweig is decisive for the innovative power, which enables a research-oriented approach in the development of new services. Innovative research possibilities are evaluated by scientists from the pharmaceutical industry, which ensures their usefulness for retrieval.
NUTRIMAG - Nutrition, Immune Function and Aging
Aging of the immune system (immune senescence) is characterized by changes in T and B cell function, which contribute to reduced immune performance and increased morbidity and mortality. This also explains why older people are at increased risk for severe courses of COVID-19. Little is known about the importance of micronutrient supply in this context. The aim of the study is to characterize the relationship between nutrition and immune function in seniors aged 70 and older and to investigate the extent to which additional micronutrient supplementation influences immune function.
CADIP - Calanus for Diabetes Prevention
Persons with chronic diseases have an increased risk of severe courses of COVID-19. This also applies to obese and diabetics. In metabolic terms, this seems to be due to the associated chronic low-grade inflammation and its consequences. This project focuses on the immunological changes in moderate overweight and a pre-diabetic metabolic state. The main question is to what extent a novel marine oil from Calanus finmarchicus has anti-inflammatory properties and can increase insulin sensitivity in prediabetics.
Nutrimmun - Immune, nutritional and health status in different dietary regimes
The diet has a significant influence on health. In addition to the dominant omnivorous food choice with comparatively high meat consumption, the vegan diet has attracted a lot of attention in recent years, although the proportion of vegans is low. On the other hand, flexitarians are also gaining in importance in terms of numbers. They eat meat, but in small quantities and depending on the situation. Up to now, comparative studies on the effects of these three nutritional patterns on nutritional and health status are lacking. There is a particular lack of data on immunocompetence. The project therefore aims to close these gaps in knowledge in order to derive recommendations for a nutritive optimization of immune performance.
Anti-COVID activity of proteasome inhibitors (argyrins)
Argyrins are peptidic natural compounds derived from soil bacteria and are characterized by a number of different activities that make them potential drugs. In addition to anti-tumor and antibiotic activities, it is especially the anti-viral properties that make argyrin a potential drug. In collaboration with physicians and virologists at the Universities of Tübingen and Heidelberg, the potential of argyrins as a drug against the coronavirus is to be investigated. The aim is to optimize the argyrins for their use against the coronavirus 2019-nCoV.