Overview of research projects

Project Details:
Mit der Untersuchung soll folgende Hypothese getestet werden: Die Impfung mit Coxevac® führt in Q-Fieber-positiven Herden zu einem verminderten Antibiotikaverbrauch im Vergleich zu nicht geimpften Q-Fieber-positiven Herden.

Funding: Niedersächsische Tierseuchenkasse Landesvereinigung der Milchwirtschaft Niedersachsen, 157.000 EUR

Project Details:
Ziel des Projekts ist die systematische Erfassung von Aufzuchtbedingungen in niedersächsischen Milchviehbetrieben mit hohen Aufzuchtverlusten und Identifizierung relevanter Risikofaktoren. Weiterhin soll ein Praxis-nahes Score-System erarbeitet werden, mit dem das Aufzuchtmanagement in einem Betrieb bewertet werden kann und welches in der Beratung benutzt werden kann.

Project Details:
Neonatal sepsis is a major risk factor for childhood mortality. The high susceptibility for septic diseases has been linked to immaturity of neonatal innate immunity. This concept primarily refers to experimental studies that found impaired inflammatory responses of neonatal innate immune cells to microbial challenges. However, one hallmark of sepsis in newborns is an extremely rapid course with a hyperinflammatory immune response. This inconsistency of experimental and clinical findings is currently unsolved indicating that the molecular mechanisms of immaturity and postnatal maturation are still unclear.
In this study we demonstrated that high levels of S100 alarmins at birth transiently induced hyporesponsiveness of phagocytes of healthy neonates compared to adult cells upon microbial challenges. The LPS response of human adult and neonatal Mo was inversely regulated resulting in differential expression of MyD88- and TRIF-dependent gene programs. Basal and LPS-induced transcription patterns in neonatal phagocytes were epigenetically regulated and adapted toward the adult phenotype during the first year of life. S100-induced programming prevented overwhelming inflammation but preserved anti-microbial activities of phagocytes. The biological and clinical relevance of this mechanism was confirmed by significantly higher lethality of S100A9-/- mice in a neonatal sepsis model and the association of lower S100A8/A9-concentrations in human neonates with the risk of septic complications. Our findings indicate that postnatal innate immune reprogramming is a vulnerable phase highly relevant for the resistance or susceptibility of newborns to hyperinflammation and septic diseases.

Results:

In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock.

Heinemann AS, Pirr S, Fehlhaber B, Mellinger L, Burgmann J, Busse M, Ginzel M, Friesenhagen J, von Köckritz-Blickwede M, Ulas T, von Kaisenberg CS, Roth J, Vogl T, Viemann D.

FASEB J. 2017 Mar;31(3):1153-1164. doi: 10.1096/fj.201601083R.

 

S100-alarmin-induced innate immune programming protects newborn infants from sepsis.

Ulas T, Pirr S, Fehlhaber B, Bickes MS, Loof TG, Vogl T, Mellinger L, Heinemann AS, Burgmann J, Schöning J, Schreek S, Pfeifer S, Reuner F, Völlger L, Stanulla M, von Köckritz-Blickwede M, Glander S, Barczyk-Kahlert K, von Kaisenberg CS, Friesenhagen J, Fischer-Riepe L, Zenker S, Schultze JL, Roth J, Viemann D.

Nat Immunol. 2017 Jun;18(6):622-632. doi: 10.1038/ni.3745. Epub 2017 May 1. Erratum in: Nat Immunol. 2017 Sep 19;18(10 ):1173.

Cooperation Partners:

Prof. Dr. Dorothee Viemann, Medizinische Hochschule Hannover

Project Details:
Studie zum Vorkommen von pathologischen Uteruserkrankungen weiblich unkastrierter Kaninchen über einen Zeitraum von März 2010 bis August 2014. Analyse von anamnestischen Daten, Röntgenbildern, sonographischen Befunden, Alter und von Ergebnissen der pathologischen und histopathologischen Untersuchung.

Results:

Evaluierung von Befunden aus Röntgen und Sonographie weiblich unkastrierter Kaninchen hinsichtlich pathologischer Uterusveränderungen

/ V. Christine Lübke. - 1. Auflage. Dissertation Stiftung Tierärztliche Hochschule Hannover

Funding: Bundesministerium für Ernährung und Landwirtschaft, 208.208 EUR

Project Details:
Ziel des Projektes ist die Entwicklung einer automatisierten Prozesssteuerung zur Quantifizierung und Regulierung in der biologischen Stufe von Abluftreinigungsanlagen (ARA) zur Reduktion von Bioaerosolen aus Schweinemastanlagen. Dazu soll mittels Time-Domain-Reflekrometrie (TDR) auf der gesamten Fläche des Filters der Feuchtegehalt quantifiziert werden. Durch die Einbindung der Messdaten in einen automatisierten Regelkreis erfolgt eine Soll-Ist-Wert-Analyse, wodurch eine über dem Filter installierte Berieselungsanlage automatisch zur Feuchteregulierung gesteuert wird. In Abhängigkeit von verschiedenen Feuchtegehalten des Filters soll eine gezielte Detektion von Bioaerosolen vor Eintritt und nach dem Austritt aus der ARA erfolgen. Es soll die Frage beantwortet werden, in welchem Zusammenhang der Abscheidegrad von Bioaerosolen aus Nutztierställen mit der Befeuchtung der biologischen Stufe der ARA steht. Durch die Variation der Stärke der Befeuchtung sollen Rückschlüsse auf die Effektivität der Filterleistung bezüglich der Bioaerosolabscheidung gezogen sowie eventuelle sekundäre Emissionen vermindert werden.

Gefördert durch das Bundesministerium für Ernährung und Landwirtschaft aufgrund eines Beschlusses des Deutschen Bundestages.

Results:

Regulating the moisture content of biofilters may enhance the efficiency of reducing bioaerosols in the exhaust air of livestock buildings. After a test period, a time-domain reflectometry (TDR) system was installed in two biofilters (paper filter, root wood filter) of a three stage filter of a pig?s house to measure the volumetric moisture content and the moisture distribution within the filters. A reduction of bacteria, fungi and endotoxins was detected in the course of seven different moisture adjustments. Low moisture led to odours and high moisture partly released relatively high concentrations of fungi. A relatively volumetric moisture content of 10 to 20% in both filters reduced the number of mesophilic bacteria and aerotolerant cocci on average to more than 90%. The endotoxin concentration was reduced from 79 to 95%. The TDR system has the potential to regulate the moisture content in paper and root wood filters which may be useful for an efficient reduction of bioaerosols.

Funding: COST (Action FA1404: Improving current understanding and research for sustainable control of the poultry red mite Dermanyssus gallinae)

Project Details:
Die EU-COST-Aktion hat zum Ziel, Bekämpfungs- bzw. Kontrollstrategien gegen die Rote Vogelmilbe zu verbessern und diese zu disseminieren. Hierfür sollen Erkenntnisse zur Milbenbiologie, Parasit-Wirt-Interaktion und neuen Bekämpfungsstrategien konsolidiert und Forschungsansätze koodiniert werden. Es soll ein "Goldstandard" zur Prophylaxe und Bekämpfung des Parasiten erarbeitet werden, der auf die einzelnen europäischen Länder und deren Produktionssysteme zugeschnitten ist.

Results:

Hubert, J., Erban, T., Kopecky, J., Sopko, B., Nesvorna, M., Lichovnikova, M., Schicht, S., Strube, C., Sparagano, O. (2017) Comparison of bacteriomes between red poultry mite populations (Dermanyssus gallinae): predominance of Bartonella-like bacteria. Microbial Ecology 74, 947-960

Funding: Europäische Kommission, 375.836 EUR

Project Details:
G-TwYST will execute rat feeding trials with GM maize NK 603 based on OECD Test Guidelines and according to EFSA considerations. In the case of maize NK603 two 90-day and a combined 2-year chronic toxicity/carcinogenicity study will be performed. By combining the results of the G-TwYST project with those of the GRACE project (90-day and 1-year study with maize MON810) it will be possible for the first time to describe the potential medium term and long term toxic effects of the two above-mentioned events. Partners will strictly comply with international standards and norms concerning feeding trials and closely collaborate with EFSA. Feeding stuff used in the trials will be produced according to the principles of good agricultural practice. The project will analyse and report the results of the feeding trials and develop recommendations on the scientific justification and added value of long-term feeding trials for GMO risk assessment. The project will ensure scientific excellence, independence and transparency of both the research process and the results. Transparency and accessibility of project plans and results is a key characteristic of the project and will be ensured by establishing a project website and by using an open access database set up by GRACE as information hubs. Results will be published as open access journal papers. Dedicated engagement, communication, and dissemination activities will target scientists, policy makers and a broad range of stakeholders. Participatory steps will be included in the planning as well as in the interpretation/conclusion phase. Moreover, the views of risk assessment and regulatory bodies as well as wider societal issues will also be taken into consideration. The results of the project will enable risk managers drawing conclusions with regard to framework of the currently applicable GM food/feed risk assessment requirements and procedures in the EU.

Funding: Deutsche Forschungsgemeinschaft, 198.000 EUR

Project Details:
In this project, we will mechanistically investigate the impact of polyphenols on the AA cascade. For this purpose we will employ liquid chromatography mass spectrometry (LC-MS) for the quantification of a comprehensive set of oxylipins of all branches of the AA cascade as targeted metabolomics approach. We will analyze the effect of polyphenols on the activity of cyclooxgenase, lipoxygenase, cytochrome P450 and epoxide hydrolase pathways of the AA cascade in different cell culture assays as well as in cell free approaches. Moreover, we will utilize the oxylipin pattern to monitor oxidative stress occurring during inflammation and its amelioration by food-born antioxidants. With these high-content screening tools, we will not only discover potentially active polyphenols, but also gain information on their mode of action, quantitative data on their potency and qualitative data on the breadth of their effects.

Funding: FAZIT-Stiftung, 35.000 EUR

Project Details:
Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal (GI) tract characterized by the onset of inflammation and tissue damage. Ample evidences suggest that IBD pathogenesis results from a multifactorial process involving genetic, environmental as well as immunogenic factors. Ulcerative colitis (UC) is an IBD characterized by the chronic inflammation of the colon. Depending on the location and extent of inflammation, UC can be referred to as: 1) ulcerative proctitis, 2) proctosigmoiditis, and 3) universal colitis. Under the last condition, another process called backwash ileitis (BWI) can result from the influx of colonic content to the ileum through an inflamed ileoceacal valve, extending thus the colitis to the terminal ileum. Gut mucosa integrity and functions such as digestion/absorption, detoxification, non-immune defensive roles and cell-cell interactions require the activities of hydrolases of the small intestinal brush border membrane (BBM) as well the presence of important basolateral membrane proteins [1, 5-9]. Alterations in the expression and activity of BBM hydrolases i.e. intestinal alkaline phosphatase (IAP), disaccharidases and aminopeptidases N (APN) have been observed in different colitis-induced animal models. Interestingly, abnormalities of the small intestine such as compromised enzymes activities and decreased intestinal cell differentiation were also observed in freshly isolated ileum from UC patients. In addition to the BBM hydrolases basolateral membrane proteins that play key roles in maintaining the integrity of intestinal cells such as mucusal mucin, E-cadherins and connexin 43 (Cx43) among others are also reported to contribute to the pathogenesis of UC.
The general aim of this project is to decipher using in vitro and in vivo models, the role of calcium signaling in ER stress and how is this could lead to a dysfunction of the intestinal epithelial cells.

Cooperation Partners:

1. Prof. Dr. Anaclet Negezahayo, Institut für Biophysik der Leibniz-Universität Hannover;

2. Prof. Dr. Marwan El-Sabban, Medical Faculty, American University of Beirut

Funding: MWK Niedersachsen / VW Stiftung, 7.400.000 EUR

Project Details:
N-RENNT (Niedersachsen Research Network on Neuroinfectiology) aims to start a neuroinfectiology research network in Lower Saxony fostering and boosting this young and important interdisciplinary field. N-RENNT will be established by implementing both focused research projects and an advanced and specific training program for graduate students. Structure-building measures as well as sustainability of the project are guaranteed by lasting support by the Speaker University (University of Veterinary Medicine Hannover, TiHo).

Cooperation Partners:

-Max Planck Institute of Experimental Medicine Göttingen, Clinical Neuroscience, Neurogenetics

-Technical University Braunschweig, Zoological Institute, Division of Cellular Neurobiology

-Institute for Experimental Infection Research, -Twincore -Center for Experimental and Clinical Infection Research -Helmholtz Center for Infection Research,Infection Genetics -University Medical Center Göttingen, Department of Neuroimmunology

- Hannover Medical School, Department for Clinical Immunology and Rheumatology,Department of Neuroanatomy

Institute of Immunology, Institute of Virology, Clinical Neuroanatomy and Neurochemistry