The Theodor Kocher Institute of the University of Bern was originally financed and built with an endowment from Theodor Kocher's Nobel prize and is now an Institute of the Medical Faculty.
Research at the Theodor Kocher Institute has a strong focus on immune cell migration during immunosurveillance and inflammation with particular emphasis on immune cell migration to different organs employing cutting-edge 3D live cell imaging.
The group of Britta Engelhardt investigates immune cell trafficking across the blood-brain barrier (BBB) into the central nervous system to delineate the cellular and molecular mechanisms involved in the migration of different immune cell subsets across the specialized BBB and blood-cerebrospinal fluid barrier (BCSFB) into the CNS during health and neuroinflammatory disorders such as multiple sclerosis or stroke.
The group of Ruth Lyck is interested in the mechanisms that control the extravasation of immune and cancer cells from the blood vessels into the central nervous system. The group established an in vitro setup to image the highly dynamic spatiotemporal behavior of immune cells or cancer cells that adhere to and extravasate across the BBB using primary mouse brain microvascular endothelial cells (pMBMECs).
With its technical platform in live cell-imaging using in vitro time-lapse videomicroscopy, intravital epifluorescence microscopy and 2-photon microscopy the TKI is part of the Microscopy Imaging Center at the University of Bern.
The group of Steven Proulx has developed novel tools using near-infrared fluorescent imaging and transgenic reporter mice to investigate the function of the lymphatic system in health and disease. A current focus is on the interactions between lymphatic vessels and the extracellular fluids of the central nervous system (cerebrospinal fluid and brain interstitial fluid) and how antigens and immune cells reach draining lymph nodes to induce immune responses in the brain and spinal cord.
The group of Joel Zindel (Department of Visceral Surgery and Medicine) studies how injuries in major body cavities are detected and repaired. This is of high biomedical importance because repair within body cavities can go awry after surgical procedures, leading to post-surgical scarring, which can cause devastating health problems. A current focus lies on the activation and migration of body cavity macrophages and mesothelial cells.
The group of Anna Oevermann at the Division of Neurological Sciences of the Vetsuisse Faculty of the University of Bern studies host-pathogen interactions in neurolisteriosis (of ruminants) including the interaction of Listeria monocytogenes with phagocytes in the brain, both endogenous populations and immigrating phagocytes. The group is interested in the attraction and immigration of neutrophils into the brain across the BBB during neurolisteriosis and their role in defense against intracerebral Listeria monocytogenes and contribution to brain damage.
The group of Curzio Rüegg at the University of Fribourg has a focus on tumor-host interactions. Specifically, Curzio Rüegg's group is using in vivo and in vitro experimental models to investigate the following aspects of tumor - host interactions:
► Tumor microenvironment: How do cells of the microenvironment and bone marrow-derived cells promote tumor invasion and metastasis? How do therapeutic interventions modify the tumor microenvironment and how do these modifications impact tumor behavior?
► Tumor angiogenesis: How do angiogenic vessels modulate tumor dormancy? How do tumors adapt to inhibition of angiogenesis?
► Tumor metastasis: How do disseminated cells interact with normal tissue at metastatic sites, in particular in the brain?
Experimental projects are complemented with clinical-translational studies aimed at validating experimental results in patients, in collaboration with various oncology centers
The group of Jens Stein is using imaging-based methods (multi-photon microscopy, optical projection tomography, selective plane illumination microscopy) in combination with multicolor flow cytometry and functional in vitro assays to "shed light" on the molecular and cellular processes that govern adaptive immune responses.
The group of Carole Bourquin at the Section of Pharmaceutical Sciences of the University of Geneva is interested in cancer immunotherapy. This is a promising and rapidly developing approach for the treatment of cancer in which the body's existing immune system is redirected against cancer cells. The discovery that synthetic short DNA and RNA oligonucleotides can be used to induce strong immune activation provides an opportunity to design new pharmacological substances to manipulate the immune system for therapeutic benefit.
Specifically, the following effects of immunostimulatory oligonucleotides and other activators of innate immunity in experimental models of cancer are investigated:
► Immune cell activation and migration: How can we activate effector cells of the immune system to recognize and destroy cancer cells? How can we target these cells to the tumor?
► Immune regulation: Tumors use many strategies to suppress and evade immune responses. How can we block these suppressive mechanisms and restore efficient antitumor immunity?
► Tumor microenvironment: How can we modify the tumor microenvironment to enhance recruitment of effector immune cells into the tumor?
The group of Christoph Scheiermann at the Département de Pathologie et Immunologie (PATIM) of the Centre Médical Universitaire (CMU) studies circadian rhythms in the immune response using an interdisciplinary approach at the intersection of immunology, biochemistry and physiology. The recruitment of leukocytes to tissues and their localization within tissues plays a crucial role in the immune response. Recruitment of leukocytes to tissues underlies a circadian, i.e daily rhythm. This supports accumulating evidence for circadian oscillations in many components of the immune system with the potential to affect disease onset and therapies.
For their studies of leukocyte migration patterns various intravital microscopy techniques in different tissues are used. Specifically, the focus is on how neural influences regulate the circadian migration of leukocytes to tissues, which promigratory factors control these rhythms and whether they can be altered by surgical, pharmacological or genetic interventions. The goal is to provide novel mechanistic insight into the systemic regulation of leukocyte trafficking with the potential for time-based, i.e. chronotherapeutic, interventions in inflammatory diseases.
The Institute for Research in Biomedicine (IRB) in Bellinzona was founded in 2000 with the clear and ambitious goal of advancing the study of human immunology, with particular emphasis on the mechanisms of host defense. Since 2009, the IRB is affiliated with the University of Italian Switzerland (USI) and some Group Leaders are also appointed Professors in Swiss or foreign Universities.
Santiago González's laboratory has a primary focus on the study the interface between pathogen and host. The laboratory research interests include the innate and adaptive immune responses to respiratory pathogens and the mechanisms by which such viruses and bacteria fight the host immune system. The initial response of the body to infection involves a series of events characterized by the rapid up-regulation and recruitment of effector molecules and cells, which facilitate the elimination of the pathogen and the restoration of homeostasis. We are currently using state-of-the-art imaging techniques such as 2-photon intravital microscopy and confocal microscopy to address some of the aforementioned mechanisms. These techniques enable the study of the interaction between the pathogen and the host in a completely new dimension, monitoring the cell-to-cell and microbe-to-cell interaction in real time. In addition, we will use some classic imaging techniques, such as electron and scanning microscopy, in order increase the resolution and structural information of the infected tissue or cell.
Valentina Cecchinato is a Research Associate at the Institute of Research in Biomedicine (IRB), and her research focuses on the mechanisms governing inflammation and its dysregulation in autoimmunity and infectious diseases. Thanks to her expertise on HIV/SIV pathogenesis and on cell trafficking, she developed an independent line of research aimed at understanding how alterations in the chemokine system could affect HIV-1 disease progression.
Marcus Thelen studied biochemistry at the University of Tübingen (DE) and received his PhD from the University of Bern in 1985. As postdoc at the Theodor-Kocher-Institute in Bern, his interests focused on inflammation and chemokines. In 1992, he received a career development award (START) from the Swiss National Science Foundation and returned to the Theodor-Kocher-Institute at the University of Bern. His laboratory worked on the molecular mechanisms of signal transduction in leukocytes, focusing on PI 3-kinase-dependent pathways and chemokine-mediated receptor activation. In 2000 he moved to Bellinzona, where he helped open the IRB and directed the Signal Transduction Laboratory working on mechanisms of chemokine mediated cell migration. Investigation the chemokine system his laboratory deorphanized two atypical chemokine receptors which regulate the availability of chemokines during homeostasis and inflammation. Marcus Thelen retired in November 2022 and is currently working as a scientific advisor.
The Institute of Cell Biology and Immunology Thurgau (BITG) in Kreuzlingen is Swiss academic research institution funded in 1999 by the Canton Thurgau in close collaboration with the University of Konstanz. The institute focuses on application-oriented basic research in the field of tumor biology, immunology and cell biology.
The group of Daniel Legler is interested in chemokine guided immune and cancer cell migration with an emphasis to understand mechanistic principles of how cells are capable of sensing guidance cues and of how chemokine receptors transmit signals across the plasma membrane to steer directional cell locomotion.
The group of Julia Gutjahr at the Institute of Cell Biology and Immunology Thurgau is interested in alternative signal transduction pathways initiated by chemotactic cytokines apart from their well-known role in cell migration. We use erythroblasts, the precursor cells of red blood cells, as a cellular model to investigate intracellular signaling of chemokine receptors.
