Project area B: functional triggers and consequences of inflammation

This project area aims for a deeper understanding of the correlation between the molecular and cellular dynamics of immune cells, environmental triggers, and the consequences of inflammation at the level of tissues and organs. An emphasis is on the multiscale imaging of local endothelial barrier function to quantitatively assess permeability to both solutes and cells. To this end, novel, scalable nanoparticle platforms, initially developed for optical and optoacoustic imaging modalities will be extended to MRI and PET imaging and applied to assess endothelial barrier integrity and track immune cells in models of inflammation. To better quantify MRI-based permeability and cell tracking approaches an integrated workflow comprised of several modalities including mass spectrometry imaging is used; and MRI is combined with dynamic PET (PET-MRI) for combined contrast-enhanced and radiotracer-based imaging to derive a quantitative 4D view of inflammatory processes in the TME. The influence of hypoxia as an important functional and environmental trigger and modulator of innate immune responses will be studied using a novel reporter mouse in a model of acute and chronic hypoxia. The long-range effects of kidney ischemic damage on lung susceptibility to infection is analysed in a two-hit model of kidney injury followed by bacterial infection. Therefore, the central immediate neutrophil activation in the lung will be exploited for the ROS-induced photoactivation of a photo-switchable protein to mark the responsive neutrophil population. Finally, optogenetics will also be used to manipulate receptor distribution in the cell membrane of immune cells and to assess downstream signalling events and their consequences on cell activation, adhesion and migration. Project Area B is tightly interlinked with Project Area A (targeting) and C (models).

Projects

  • PEP-2023-02: Multi-scale, model-driven image reconstruction of the tumor micro-environment
    Principal investigator: Christian Engwer (Institute for Applied Mathematics: Analysis and Numerics)
    Project term: 07/2023–06/2024
  • CS-2021-02 – Chemokine receptor CXCR4 in the development of hepatic vascularization and congenital portosystemic venous shunting
    (related to CRC project B04)
    Clinician scientist: Stefanie Bobe (Gerhard-Domagk Institute of Pathology & European Institute for Molecular Imaging)
    Scientific and clinical mentors: Friedemann Kiefer, Eva Wardelmann
    Project term: 01/2022 - 12/2024