SFB 1450:  Multiscale imaging of organ-specific inflammation

Inflammation is a rapid and highly effective defence reaction of the immune system to a variety of harmful stimuli, including infections, tissue damage, autoimmune activities, or cancerous growth. Mechanisms involved limit tissue damage and are important for healing. However, dysregulated inflammation can lead to excessive, chronic, or sometimes suppressed immune responses, playing a significant role in the onset of widespread diseases such as sepsis, rheumatoid arthritis and cancer. Therefore, inflammation must be precisely controlled and timely terminated. Despite intensive research, we lack a holistic view that integrates the myriad of biological processes occurring during inflammatory responses, particularly in terms of their spatial and temporal coordination both locally and systemically, and how these processes are interconnected functionally. This emphasizes the requirement for a currently non-existing in vivo imaging technology, covering various temporo-spatial scales, from molecules over cells to model organisms and patients, i.e., multiscale imaging. In the first funding period, we successfully brought together an interdisciplinary team of clinicians and natural scientists, highly capable of developing and applying innovative in vivo imaging strategies. Inflammatory scenarios were evaluated in first multiscale immune imaging approaches, covering broad temporo-spatial scales ranging from molecular pathways to whole body processes. Methodological projects have laid a robust foundation of chemical, technological and mathematical methods for the detailed visualisation and analysis of the dynamics and interplay of distinct inflammatory cell populations. At the same time, biomedical projects studied molecular pathways during dysregulated immune responses in disease models and patients. Together, we have developed and applied methods to generate, visualize and analyse first multiscale imaging data sets from experimental data of various projects. This also provided an excellent basis for training and promotion of doctoral researchers and Medical and Clinician Scientists at different stages of their careers. In the forthcoming funding period scientists focussing on methodology will refine, combine, and expand their foundational work. These advancements will allow to adapt multiscale imaging to more complex and dynamic preclinical inflammatory models mimicking sepsis, heart and kidney infarction, tumours, allergies, and autoimmune diseases. Our studies will thereby contribute to a better understanding of the interplay between molecular regulators and immune cells at local sites of inflammation in vivo that distinguishes and determines productive versus destructive inflammation. Our ultimate goal is to translate multiscale immune imaging into novel diagnostic tools for patients and to apply imaging to guide existing and emerging therapies.

DFG Programme Collaborative Research Centres

• A01 - Cell-type specific multiscale imaging of leukocytes through the combination of protein tagging and radiochemical labelling (Project Heads Konken, Christian Paul ;  Mootz, Henning D. ;  Rentmeister, Andrea )
• A02 - Tailored coordination compounds as multimodal labels for multiscale imaging (Project Heads Bobe, Stefanie ;  Strassert, Cristian Alejandro )
• A03 - Targeting of S100A8/A9 for imaging of inflammatory disorders (Project Heads Faust, Andreas ;  Fritz, Günter )
• A04 - Metabolic targeting of bacteria through complex carbohydrates and siderophores (Project Heads Faust, Andreas ;  Gilmour, Ryan ;  Niemann, Silke )
• A05 - Targeting immune cell dynamics by longitudinal whole-body imaging and mathematical modelling (Project Heads Schäfers, Klaus ;  Wirth, Benedikt )
• A06 - Improving intravital microscopy of inflammatory cell response by active motion compensation using controlled adaptive optics (Project Heads Huser, Thomas ;  Wirth, Benedikt )
• A07 - Image-guided tumour therapies with CAR T cells co-engineered for local depletion of immunosuppressive macrophages (Project Head Rössig, Claudia )
• B01 - Quantitative assessment of endothelial permeability by novel scalable BODIPY nanostructures (Project Heads Fernandez-Huertas, Gustavo ;  Masthoff, Max )
• B02 - Quantitative MRI of organ-specific vascular permeability and immune cell dynamics by combination with mass spectrometric imaging (Project Heads Faber, Cornelius ;  Karst, Uwe )
• B04 - Multiscale visualisation and analysis of innate immune cell migration at sites of hypoxic inflammation in vivo (Project Heads Kiefer, Friedemann ;  Risse, Benjamin )
• B05 - Mechanisms and visualization of kidney injury-associated immunomodulatory responses affecting susceptibility to bacteria-induced pulmonary infection (Project Heads Block, Helena ;  Wegner, Seraphine ;  Zarbock, Alexander )
• B06 - Dynamic PET-MRI for integrated quantification of molecular immune responses and their vascular consequences (Project Heads Backhaus, Philipp ;  Büther, Florian )
• B07 - Targeting plexin signalling and its role in immune modulation (Project Head Sánchez, Maria Florencia )
• C01 - Metabolic priming of monocytes during inflammation in vivo (Project Heads Roth, Johannes ;  Schäfers, Michael )
• C02 - Phagocyte responses during apoptotic cell clearance in the resolution of inflammation (Project Head Alonso Gonzalez, Noelia )
• C03 - Targeting S100A8/S100A9 induced MDSCs in inflammatory disorders (Project Heads Hermann, Sven ;  Vogl, Ph.D., Thomas )
• C05 - The role of CSK in the regulation of immune cell recruitment and metabolism during acute kidney injury (Project Heads Hörr, Verena ;  Margraf, Andreas ;  Reuter, Stefan )
• C06 - Nanocarrier-based functional analysis of myeloid cells in inflammatory and autoimmune skin diseases (Project Heads Landfester, Katharina ;  Steinbrink, Kerstin )
• C07 - Imaging of immune cell dynamics and host-pathogen interactions in gut-associated lymphoid tissue during Yersinia pseudotuberculosis infections (Project Heads Dersch, Petra ;  Rossaint, Jan )
• C08 - Multiscale imaging of mechanisms underlying mast cell-dependent inflammation (Project Heads Lämmermann, Ph.D., Tim ;  Rambold, Angelika )
• INF - Research data management and infrastructures for visualization, analysis and sustainable software development (Project Head Vogl, Raimund )
• MGK - Integrated Research Training Group (IRTG) Multiscale Imaging (Project Head Kiefer, Friedemann )
• Z01 - Interactive and computational analysis of large multiscale imaging data (Project Heads Jiang, Xiaoyi ;  Linsen, Lars )
• Z02 - Central tasks of the Collaborative Research Centre (Project Head Schäfers, Michael )

• B03 - Regulation of vascular permeability and leukocyte extravasation in inflammation: mechanisms and heterogeneity in different organs (Project Head Vestweber, Dietmar )
• C04 - Dynamic imaging and molecular mechanisms of myeloid cell infiltration into the inflamed peritoneum (Project Head Sorokin, Lydia )

Applicant Institution Universität Münster

Participating University Universität Bielefeld; Universität Hohenheim

Participating Institution Max-Planck-Institut für Polymerforschung

Spokesperson Professor Dr. Michael Schäfers