Overview of research projects

Funding: DFG, 210.330 EUR

Clinics/Institutes:
Institute of Zoology
Institute for Pathology

Project Details:
Aposematism is the association between a bright warning colouration and a defence mechanism, (e.g. toxins) for avoiding predation. The genetics of colouration and toxicity in aposematic animals is still not well investigated. In this context, the diversity of alkaloids in the skin and colouration patterns linked to predator avoidance strategies in Neotropical poison frogs is an exciting opportunity to study the convergence of ecological adaptation. Poison frogs differ in colouration patterns and toxicity among populations and strong evidence exists that aposematism is adaptive, probably driven by predator selection. For the strawberry frog Oophaga pumilio, we were able to show that genes related to pigment metabolism (e.g. pteridinene) are differently expressed between color morphs. The next objective is to connect the structure of cells containing pigment (chromatophores), the chromatographic characterization of color pigments and alkaloids, expression patterns of genes that are involved in coloration and toxicity for three color-polymorphic, neotropical poison dart frogs of the genus Oophaga.

For our project, we will collect skin and liver samples from eight populations with either green or red colouration in Panama and Costa Rica. Together with collaborators from the University of Costa Rica, the TiHo, the University of Cambridge and STRI in Panama we will characterize the chromatophores in the skin by electron microscopy, analyse the colour pigments and toxins in the skin by gas chromatography, and will perform RNAseq analysis on dorsal skin-derived cDNA. We expect that expression levels of genes in pigment (e.g. carotenoid pathways) and alkaloid metabolism to vary among different colour morphs (red vs. green) but to be similar within colour morphs across species due to convergence. Our study will lead to a better understanding of the link between geno- and phenotypes of adaptive anti-predator strategies and illuminate the evolution of regulatory mechanisms of gene expression.

Cooperation Partners:

Dr. Giselle Tamayo, UCR, Costa Rica

Dr. Beatriz Willink, UCR, Costa Rica

Dr. Nicolas Mundy, University of Cambridge, UK

Dr. Roberto Ibañéz, STRI, Panama

Funding: EU Kommission (HORIZON 2020), 405.001 EUR

Clinics/Institutes:
Research Center for Emerging Infections and Zoonoses

Project Details:
MERMAID proposes to further develop tissue-based in vitro mucosa models and assays to serve as in vitro models for
infection and to study immune protection with selected immune components. As such, the models will consist of a pathogenmucosal interface with a third dimension added, i.e. the interaction with selected immune mediators mimicking a relevant
(protective) natural immune response that can or should be obtained by vaccination. The models that will be developed will
also account for the heterogeneity existing in the population. The resultant next-generation mucosal tissue models will then
be validated using specimens derived from controlled human infection model (CHIM) studies and natural infections to
confirm the relevance of the model for the in vivo situation and the selected immune mediators. Subsequently, samples from
vaccine trials will be used to assess the induction of these immune responses in vivo and prove their efficacy ex vivo in next
generation models.

Funding: Gesellschaft für Kynologische Forschung, Hahn-Stiftung, DFG, DAAD, 30.000 EUR

Clinics/Institutes:
Small Animal Clinic

Project Details:
Die Untersuchung des Liquor cerebrospinalis ist ein wertvolles Instrument, um in vivo Informationen über den Zustand des zentralen Nervensystems zu erhalten. Die darin enthaltenen Zellen reflektieren zumindest teilweise die perivaskuläre Zellpopulation im ZNS. Es wurde daher eine Methode entwickelt, diese Zellen mit Hilfe der Durchflusszytometrie zu charakterisieren. Derzeit werden die Toll-like Rezeptoren näher bestimmt.
In einer 2. Studie wird untersucht, wie sich die Glukose im Liquor cerebrospinalis des Hundes verhält, und ob die Bestimmung von dieser zur Diagnostik beitragen kann oder sich proportional zur Zellzahl bzw. zur Blutglukose verhält.
In weiteren Studien werden verschiedene Biomarker, wie Tau-Protein, Chemokine, Zytokine und Abbauprodukte von Gliazellen und Nervenzellen untersucht, um einen prognostischen Faktor für Rückenmarkserkrankungen zu erhalten. Neue Methoden zur Haltbarmachung der Zellen werden evaluiert.

Funding: teilweise BMBF (Lichtenbergstipendium); Gesellschaft für Kynologische Forschung; Irene und Hans-Joachim Hahn-Stiftung, DAAD, 80.000 EUR

Clinics/Institutes:
Institute for Pathology
Small Animal Clinic

Project Details:
Die steril-eitrige Meningitis-Arteriitis des Hundes (SRMA)ist die häufigste entzündliche Erkrankung des zentralen Nervensystems des Hundes im Norddeutschen Raum. Mit Hilfe mehrerer Pathogenesestudien soll versucht werden, die Erkrankung besser zu charakterisieren, um neue Therapiestrategien entwickeln zu können. Die Zellpopulation in Liquor cerebrospinalis und Blut wurde mit Hilfe durchflusszytometrischer Studien charakterisiert. Studien zur Zytokinexpression sollen helfen, das Phänomen der hohen IgA Produktion zu erleuchten. Die Untersuchung von Toll-like Rezeptoren soll einen Hinweis auf die Ätiologie der Erkrankung liefern. Die Th17 Antwort, NETs und das Endocannabinoidsystem werden näher untersucht

Results:

Arianna Maiolini, Regina Carlson, M. Schwartz, G. Gandini and Andrea Tipold: "Determination of immunoglobulin A concentrations in the serum and cerebrospinal fluid of dogs: An estimation of its diagnostic value in canine steroid-responsive meningitis-arteritis." The Veterinary Journal, 191, 219-224, 2012

 

S.A. Moore, M.Y. Kim, Arianna Maiolini, Andrea Tipold and M.J. Oglesbee: "Extracellular hsp70 release in Canine Steroid Responsive Menintis-Arteritis." Vet Immunol Immunopathol., 145, 129-133, 2012

 

Arianna Maiolini, Regina Carlson and Andrea Tipold: "Toll-like receptors 4 and 9 are responsible for the maintenance of the inflammatory reaction in canine steroid-responsive meningitis-arteritis, a large animal model for neutrophilic meningitis." J Neuroinflammation 9, 226 (1-12), 2012.

 

Arianna Maiolini, M. Otten, M. Hewicker-Trautwein, R. Carlson and Andrea Tipold: "Interleukin-6, vascular endothelial growth factor and transforming growth fator beta 1 in canine steroid responsive meningitis-arteritis." BMC Veterinary Research, 9:23, 1-10, 2013.

 

J. Freundt-Revilla, A. Maiolini, R. Carlson, M. Beyerbach, K. Rentmeister, T. Flegel, A. Fischer and Andrea Tipold: "Th17 skewed immune response and cluster of differentiation 40 ligand expression in canine steroid-responsive meningitis-arteritis, a large animal model for neutrophilic meningitis." J. Neuroinflammation 14:20, 2017. doi.10.1186/s12974-016-0784-3.

Funding: Deutsche Forschungsgemeinschaft (DFG) , 404.650 EUR

Clinics/Institutes:
Institute for Virology

Project Details:
The genus Pestivirus belongs to the virus family Flaviviridae and comprises RNA viruses of great relevance, like Bovine viral diarrhea virus (BVDV) and Classical swine fever virus (CSFV), which are causative pathogens of notifiable diseases. Since decades, it was commonly accepted that pestivirus infections are restricted to cloven hooved (ungulate) hosts. In the past years, several atypical pestiviruses have been discovered in non-ungulate hosts. These newly discovered pestiviruses show the typical genome organization, but are genetically highly distinct. Obviously, these novel viruses represent a new group within the pestiviruses with so far uncharacterized biological properties. In addition, such a novel pestivirus was also discovered in pigs and designated "atypical porcine pestivirus" (APPV). APPV causes a neurological disease in newborn piglets (congenital tremor) and involvement in other diseases (e.g. infertility, abortion, neonatal malformations) appears likely.
Within this research project, it was possible to adapt APPV to cell culture conditions and to propagate it. The availability of a virus isolate provided the basis for further studies to characterize the biological properties of the pathogen. Our work demonstrated that there are obviously significant differences in the cell entry of APPV and CSFV. It has been believed for long time that the complement-regulating protein CD46 is the key for pestiviruses to penetrate the host cell, but our work showed that some pestiviruses - including CSFV - use a CD46-independent mechanism for cell entry. Which cellular surface structures are used instead for cell entry is still unclear and will be the subject of further research.
The aim of the study is to provide insights into the complex, probably multi-step process of cell entry. Within this project is the aim to identify the molecular determinants of cell entry of pestiviruses and to characterize them in more detail. Several host cell factors have already been identified which apparently interact with the viral envelope proteins during early phases of viral replication and can influence virus replication. First, it has to be elucidated whether these factors directly interact with the virus particles or whether these are indirect effects, e.g. caused by binding to other cellular proteins or by an altered cell metabolism. Knowledge of the key factors for the entry of porcine pestiviruses into the host cell can make a valuable contribution to understanding the biology of the new and widespread pathogen in the pig population, APPV, as well as the properties of the long-known animal disease pathogen CSFV.

Funding: BfN, 1.721.249 EUR

Clinics/Institutes:
Institute for Terrestrial and Aquatic Wildlife Research

Project Details:
As top predators, marine mammals are an important component of marine ecosystems. They are under increasing pressure from anthropogenic activities such as fisheries, offshore wind energy development, shipping traffic, etc. The survey and assessment of their populations and precise knowledge of their distribution patterns, habitat requirements and population trends are prerequisites for their effective protection and sensible protected area management.
Within the framework of this project, the collection of new data along the analysis of existing data sets will contribute significantly to the knowledge required for the consideration of fundamental ecological relationships and are of high scientific value. Habitat-based models are used to investigate which abiotic, biotic and anthropogenic factors fundamentally influence the occurrence and distribution of marine mammals. Population dynamics models will provide information on the influence of various stressors on the development of harbour porpoise populations. These models will provide simulations of future population trends assuming different pressures from anthropogenic stressors and can, thus, inform the development of adequate management measures. HABITATWal will also integrate the German contribution to the international SCANS-IV survey in summer 2002, when regionally coordinated visual surveys in the shelf and offshore waters of the European Atlantic will be conducted to generate robust abundance estimates for regularly occurring cetacean species. Detailed information on the acoustic and visual occurrence and density of minke whales and other cetacean species will be collected through a dedicated shipboard survey on the Dogger Bank and an annual monitoring will be developed. In addition, the expansion of the recording methods in large-scale monitoring is to be accompanied scientifically. This also includes a feasibility study on the possible addition of a passive-acoustic monitoring (PAM) network in the German North Sea.

Funding: Stipend Thailand Government via Kasetsart University , 143.168 EUR

Clinics/Institutes:
Institute for Physiology and Cell Biology
Small Animal Clinic

Project Details:
Neue Erkenntnisse zeigen, dass die Mikrobiom-Darm-Hirn-Achse einen wichtigen Einfluss auf die Hirngesundheit haben kann. Ein Ungleichgewicht der Darmflora könnte unkontrollierbare Epilepsien begünstigen. In unserer Studie transplantieren wir geeignete Darmflora an Patienten, bei denen Antiepileptika nicht wirken.Während der Studie sammeln wir Kot, Urin und Speichel und testen Anfallsfrequenz und Verhaltensaspekte der Hunde.

Funding: EU-Interreg, Bavarian Nordic, 270.000 EUR

Clinics/Institutes:
Institute for Parasitology (Dept. of Infectious Diseases)

Project Details:
Ticks transmit various human and animal pathogens. With regard to pathogens, the vector function of ticks for the causative agent of Lyme borreliosis (Borrelia burgdorferi sensu lato complex), human and animal granulocytic anaplasmosis and tick-borne encephalitis (TBE virus) is of particular importance. Studies on the abundance and distribution of ticks and their pathogens are therefore essential for assessing the One Health risk. Regarding tick-transmitted pathogens, this project collects data not only for Germany but also at the international level.

Results:

Bajer, A., Beck, A., Beck, R., Behnke, J.M., Dwużnik-Szarek, D., Eichenberger, R.M., Farkas, R., Fuehrer, H.-P., Heddergott, M., Jokelainen, P., Leschnik, M., Oborina, V., Paulauskas, A., Radzijevskaja, J., Ranka, R., Schnyder, M., Springer, A., Strube, C., Tolkacz, K., Walochnik, J. (2022) Babesiosis in Southeastern, Central and Northeastern Europe: An emerging and re-emerging tick-borne disease of humans and animals. Microorganisms 10, 945

 

Springer, A., Lindau, A., Probst, J., Drehmann, M., Fachet, K., Thoma, D., Vineer, H.R., Noll, M., Dobler, G., Mackenstedt, U., Strube, C. (2022) Update and prognosis of Dermacentor distribution in Germany: Nationwide occurrence of Dermacentor reticulatus. Frontiers in Veterinary Science 9, 1044597

 

Springer, A., Jordan, D., Glass, A., Kahl, O., Fingerle, V., Girl, P., Chitimia-Dobler, L., Strube, C. (2020) Borrelia infections in ageing ticks: Relationship with morphometric age ratio in field-collected Ixodes ricinus. Microorganisms 10, 166

 

Knoll, S., Springer, A., Hauck, D., Schunack, B., Pachnicke, S., Strube, C. (2021) Regional, seasonal, biennial and landscape-associated distribution of Anaplasma phagocytophilum and Rickettsia spp. infections in Ixodes ticks in northern Germany and implications for risk assessment at larger spatial scales Ticks and Tick-Borne Diseases 12, 101657

 

Hauck, D., Jordan, D., Springer, A., Pachnicke, S., Schunack, B., Fingerle, V., Strube, C. (2020) Transovarial transmission of Borrelia spp., Rickettsia spp. and Anaplasma phagocytophilum in Ixodes ricinus under field conditions extrapolated from DNA detection in questing larvae. Parasites & Vectors 13, 176

Cooperation Partners:

Dr. O. Kahl, tick-radar GmbH

Prof. Dr. U. Mackenstedt, Universität Hohenheim

Dr. V. Fingerle, Nationales Referenzzentrum für Borrelien, Oberschleißheim

Prof. Dr. G. Dobler, Nationales Konsiliarlabor für FSME, München

Dr. L. Chitimia Dobler, Institut für Mikrobiologie der Bundeswehr, München

Clinics/Institutes:
Institute for Parasitology (Dept. of Infectious Diseases)

Project Details:
Ticks of the genus Ixodes transmit various human and animal pathogens. In this long-term project running since 2005, pathogen prevalence in ticks in the city of Hannover, Germany, is monitored to investigate potential effects of climate change. In addition to the infection status of the ticks, the tick density in the Hannover area will also be determined.

Results:

Glass, A., Springer, A., Raulf, M.-K., Fingerle, V. Strube, C. (2023) 15-year Borrelia prevalence and species distribution monitoring in Ixodes ricinus/inopinatus populations in the city of Hanover, Germany. Ticks and Tick-Borne Diseases 13, 102074

 

Glass, A., Springer, A., Strube, C. (2022) A 15-year monitoring of Rickettsiales (Anaplasma phagocytophilum and Rickettsia spp.) in questing ticks in the city of Hanover, Germany. Ticks and Tick-Borne Diseases 13, 101975

 

Hauck, D., Springer, A., Chitimia-Dobler, L., Strube, C. (2020) Two-year monitoring of tick abundance and influencing factors in an urban area (city of Hanover, Germany). Ticks and Tick-Borne Diseases 11, 101464

 

Blazejak, K., Raulf, M.-K., Janecek, E., Jordan, D., Fingerle, V., Strube, C. (2018) Shifts in Borrelia burgdorferi (s.l.) geno-species infections in Ixodes ricinus over a 10-year surveillance period in the city of Hanover (Germany) and Borrelia miyamotoi-specific Reverse Line Blot detection. Parasites & Vectors 11, 304

 

Blazejak, K., Janecek, E., Strube, C. (2017) A 10-year surveillance of Rickettsiales (Rickettsia spp. and Anaplasma phagocytophilum) in the city of Hanover, Germany, reveals Rickettsia spp. as emerging pathogens in ticks. Parasites & Vectors 10, 588

Cooperation Partners:

Dr. V. Fingerle, Nationales Referenzzentrum für Borrelien, Oberschleißheim

Funding: Drittmittelprojekt, gefördert durch die Fritz-Ahrberg-Stiftung., 100.000 EUR

Clinics/Institutes:
Institute for Food Quality and Food Safety

Project Details:
The consumption of short-ripened and nitrite-reduced raw sausages can pose a risk to the consumer if a lack of drying and altered ripening processes allow pathogenic and spoilage-causing bacteria to multiply. Bacillus species are used as starter cultures in modern biotechnological processes, but also in traditionally fermented products. They are able to form so-called bacteriocins. These are ribosomally synthesised peptides with a high antibacterial activity. An application of these bacteriocins in sausage production can extend the shelf life and prevent the occurrence of pathogenic germs. As starter cultures, bacteriocin-forming bacteria can make an important contribution to the safe production of short-ripened and nitrite-reduced raw sausages.
In this project, Bacillus species that have not been investigated so far are tested for their antimicrobial properties against meat-relevant spoilage and zoonotic pathogens (e.g. Campylobacter spp., listeria and salmonella). With an already established high-throughput method on a laboratory scale, this can be done with a hundred isolates simultaneously. Cell-free culture supernatants are obtained, which are subsequently used to identify the potential bacteriocins. Promising Bacillus isolates are tested in a second step in short-ripened and nitrite-reduced raw sausage products as a supplement to established starter cultures.