CRC 1450: Multiscale Imaging of Organ-Specific Inflammation (inSight)

Basic data for this project

Description

Inflammation is a common, fast and innate response of the immune system to sterile or infectious tissue damage or autoimmune triggers. It aims at minimising tissue destruction and maintaining organ function, hence is vital to life. Yet, overshooting or chronic inflammation is a frequent severe cofactor in the development of widespread diseases. The last decades have seen significant progress in understanding the principal pathways leading to inflammatory processes. However, organ-specific properties of inflammatory diseases and the local dynamics of innate immune cell action and interactions remain poorly investigated. Important questions are the extent and functional relevance of innate immune cell polarisation in vivo and the consequences of local effector functions for migration dynamics and, hence, the course of organ-specific inflammation. In addition, recent single cell RNA sequencing data has revealed significant vascular heterogeneity in different tissues and organs, the effect of which on inflammation have not been addressed to date. CRC inSight brings together an interfaculty team of scientists with the aim of understanding the cellular and molecular basis of inflammation in different tissues and in response to different insults through the development of innovative tools and new cellular and molecular in vivo imaging strategies. Through detailed spatial and temporal analyses, we will investigate the dynamics and plasticity of distinct immune cell populations. We will image their penetration of endothelial barriers, their activation at sites of inflammation, and their contribution to tissue damage, and hence, generate novel insights into the complex innate immune response to sterile and infectious noxes in whole organisms. Intravital and dynamic visualisation of cellular and molecular processes using high-resolution optical and whole-body imaging are central to our approach. We will generate so far unavailable multiscale image data sets through novel methodological strategies that integrate information from imaging modalities across spatial and temporal scales. This will involve genetic and chemical biology-based targeting of immune cells and bacteria combined with new versatile labels for visualising the same molecular mechanism using imaging modalities at different scales. A mathematical and computational strategy will be applied to bridge scales, interactively visualize multiscale data sets and for pattern recognition. The methods developed by this CRC will be applied to preclinical inflammatory models mimicking diseases such as heart and kidney infarction, autoimmune disease and infection. Our studies will promote 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.