The main research field of the Clinical Immunology Group is the pathogenesis of equine allergic diseases, in particular of equine insect bite hypersensitivity (IBH). We have shown that IgE-mediated reactions play an important role in this disease and the relevant Culicoides allergens have been characterized at the molecular level and expressed as recombinant proteins. With functional in vitro studies we have shown that IBH is characterized by an imbalance between the regulatory and T-helper 2 immune response. First vaccination studies using these recombinant allergens and various adjuvants indicate that the immune response of Culicoides unexposed horses (living in Iceland) can be directed toward a T-helper 1/regulatory immune response and that this approach could be used for preventive allergy immunization and allergen immunotherapy. The focus of our future research is the further development of allergen immunotherapy in horses and the study of the role of dendritic cells and keratinocytes in the development of IBH. This will be performed in collaboration with the Division of Immunology, IVI, at our Faculty and with Prof . Eliane Müller (Dermfocus).
We aim at the identification of the causative mutations for hereditary phenotypes. The breeding practices in domestic animals with closed populations and a certain degree of inbreeding favor the appearance of new recessively inherited traits, which can be desirable, but may alternatively also represent genetic defects. Thus, domestic animals provide a unique reservoir of spontaneous mutants, whose molecular analysis can contribute to basic biomedical science and to sustainable breeding programs that improve the health and wellbeing of domestic animals. New technologies, such as genome-wide association studies (GWAS) or whole genome sequencing (WGS) greatly facilitate our research. Some of the traits that we study are not directly related to the four research priority foci at the faculty and their investigation is then categorized as independent project.
Institute of Genetics
Small Animal Orthopedics
We look into the pathophysiology of cranial cruciate ligament disease in dogs. Our main interest is focused on the interaction between intraarticular structures and ligament homeostasis. Ligamentocytes are responsible to keep an equilibrium between matrix production and matrix degeneration. Mediators produced from articular tissues, for example inflammatory products from the fat pad, influence the activity of ligamentocytes and might be responsible for increased but controlled cell death in the ligament. Identifying such pathways allows ultimatively to evaluate novel treatment strategies to control chronic degenerative changes within the ligament.
Small Animal Surgery
Veterinary Pharmacology & Toxicology
A. Identification and characterization of cytochrome P450 enzymes (CYPs) and species differences
B. Opportunities and risks of nanomaterials – Biomedical applications.
Ad A: In contrast to humans, to date, only sparse information about equine cytochrome P450 enzymes (CYPs) involved in drug metabolism is available. The project includes identification, and characterisation of CYPs as well as research related to pharmacogenetics. The obtained knowledge is important for drug metabolism will provide a basis for studying drug-drug interactions in horses and greatly enhance our ability to prevent failure of therapy and adverse effects. Expression levels of the identified CYPs are investigated in equine liver and in primary hepatocytes incubated with and without the potential inducer rifampicin using RNA sequencing, a new technology that allows to also identify mRNA transcripts that are yet unknown. In silico analyses, namely three dimensional homology models (3D) of CYP3A isozymes, will be built to model protein sites relevant for ligand binding.
Ad B: Our research focuses on the study of biodistribution and biological effects of nanoparticles (NPs) released from biodegradable brain implants to evaluate possible health risks. Special emphasis is put on how laser-irradiated NPs interact with brain cells and tissue and how size and shape of the NPs influence the cell-interaction. We use state of the art models including neuronal cell lines, primary cells and organotypic brain slices to investigate nanoparticle uptake and the underlying mechanisms and possible toxicity. Our study will gain insight in size-dependent and nano-specific characteristics of cellular uptake of NPs in neuronal cells and brain tissue after release from a biodegradable implant, a field hardly explored and only poorly understood. The results will be made available to the authorities for decision-making with regard to NP regulations.
Division of Veterinary Pharmacology & Toxicology
We aim at the understanding of the mechanisms through which aquatic contaminants interfere with the fish immune system. Emphasis is given on chemical effects that are mediated via endocrine receptors, in particular arylhydrocarbon receptors (AhR), membrane-bound and nuclear estrogen receptors (ER), and thyroid receptors (TR). The research questions addressed by our group iare (i) which immune cell types express AhR, ER or TR?, (ii) which immune cell functional changes are induced by the ligand-dependent activation of these receptors?, (iii) does the contaminant-related immunomodulation translate into altered immunocompetence and pathogen resistance of the fish?, and (iv) to what extent does the physiological status of the fish (developmental stage, reproductive cycle, nutritional status, stress) influence the receptor-mediated immunomodulating effects of environmental contaminants? Experimentally, we rely on two model fish species, rainbow trout and zebrafish, and we use both in vitro and in vivo approaches. The research is funded by the Swiss National Science Foundation and the European Commission.
Centre for Fish and Wildlife Health
Disease ecology refers to the study of host-pathogen interactions within the context of their environment and evolution. To understand the universal role of pathogens in ecosystems, pathogen transmission and spread in both time and space and the impact on host populations are key features. Besides emerging diseases, which are often invasive species, outbreaks of infections can often be caused by environmental factors affecting the hosts and/or the pathogens singly and/or in combination (e.g. temperature, agro-chemicals). Therefore, understanding the incidence and impact of diseases requires understanding of the ecological conditions and their interactions.
At the Vetsuisse Faculty Bern, disease ecology questions are addressed in the research on bees, fish, and wildlife.
Bees and other insects, provide crucial ecosystem services for human food security and maintenance of biodiversity. It is therefore not surprising that major declines in wild insects, combined with losses of managed bees, have recently raised great concern.
Diseases are playing an apparent key role for the disastrous health situation of managed European honey bee subspecies, Apis mellifera, globally. In particular, the ubiquitous ectoparasitic mite Varroa destructor, an invasive species from Asia, is the primary biological cause of managed honey bee colony mortality worldwide. This is mainly because it is a very efficient vector of several honey bee viruses, generating a disease epidemic within the colony, which dwindles until it dies. Other disease are also involved, e.g. small hive beetles Aethina tumida or microsporidians Nosema ceranae. Theses pathogens originally described from honey bees can spill over to other species, e.g. bumblebees, Bombus spp. The extent and role of such pathogen spill over for the decline of wild species is not well understood at present. Likewise, the role of interactions between factors from the individual bee, over the colony and apiary to the landscape level is not clear as are the mechanisms behind those interactions.
Our hypothesis-driven research therefore aims to better understand the basic biology of both bee hosts and their pathogens in order to shed light on the fundamental mechanisms underlying the impact of disease on ecosystem service providing insects.
The myxozoan parasite, Tetracapsuloides bryosalmonae, has a multi-host life cycle, involving both vertebrae (cold-water salmonids) and invertebrate (bryozoan) hosts. In salmonids, T. bryosalmonae causes the proliferative kidney disease (PKD) of cold-water salmonids. Recent studies suggest that PKD is an emerging disease in Europe and Northern America, and that the emergence is linked to increasing temperatures and eutrophication. Our research incorporates ecological, genetic, immunological and epidemiological studies across the entire life-cycle (fish and bryozoans) of the disease agent to understand disease maintenance, emergence and spread in river networks and to create predictions for scenarios of future environmental change in aquatic systems. The research is funded by SNF-Sinergia.
A number of infectious diseases such as bovine tuberculosis, sarcoptic mange, canine distemper, infectious keratoconjunctivitis of wild Caprinae or leptospirosis may be maintained in free-ranging wildlife populations. Pathogen maintenance in the wild represents a potential threat to wildlife conservation, domestic animal and human health. There are strong indications that animal densities, game management strategies and climatic factors are drivers of infection dynamics in wildlife populations. We carry out harmonized epidemiological investigations in wildlife populations in different Swiss and European regions with various disease patterns and host abundance to track the anthropogenic and natural environmental factors contributing to disease emergence and maintenance in the wild. In the framework of multidisciplinary collaborations, we also investigate host and pathogen factors and merge the results obtained with different approaches to perform integrative data analyses, with the aim of formulating recommendations for disease prevention and control. The research is supported by the Federal Food Safety and Veterinary Office, the Federal Office of Environment, EMIDA-Eranet, COST, and additional funding sources.
Centre for Fish and Wildlife Health / Institute of Bee Health
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