Multiscale visualisation and analysis of innate immune cell migration at sites of hypoxic inflammation in vivo

Project number: CRC 1450 B04
Project term: 01/2021–12/2024

Graphical abstract
© CRC inSight

Hypoxia is an efficient inducer of inflammation, resulting in immune cell invasion into the oxygen-deprived tissue. Accumulation of metabolically highly active immune cells increases oxygen consumption, aggravating hypoxia and tissue damage. The aim of this project is to generate new hypoxia reporters (1) and reporter mouse lines (2) based on the oxygen-independent fluorescent protein UnaG, as well as metabolic reporters (3), which will be functionally tested and applied in preclinical models of myocardial infarction (4), kidney ischemia and intestinal infection.

Using probabilistic machine learning on the imaging data generated, we will attempt to analyse quantitatively tissue hypoxia across multiple imaging scales (5) with a particular focus on the explainability of our deep learning models (6) to ensure trustworthy predictions. These insights will feed back into the sensor design and reporter mouse generation to further optimise our multi-scale analysis of hypoxia, metabolism and cell migration.

Project leaders


The names of the principal investigators in our network have been bolded. Publications released prior to 2021, when funding for our network commenced, represent previous project-related work.


Kong C, Bobe S, Pilger C, Lachetta M, Oie CI, Kirschnick N, Monkemoller V, Hubner W, Forster C, Schuttpelz M, Kiefer F, Huser T, Schulte Am Esch J. Multiscale and Multimodal Optical Imaging of the Ultrastructure of Human Liver Biopsies. Front Physiol 2021;12: 637136. Abstract


Bian A, Jiang X, Berh D, Risse B. Resolving colliding larvae by fitting ASM to random walker-based pre-segmentations. IEEE/ACM Trans Comput Biol Bioinform 2019: epub. Abstract


Hägerling R, Hoppe E, Dierkes C, Stehling M, Makinen T, Butz S, Vestweber D, Kiefer F. Distinct roles of VE‐cadherin for development and maintenance of specific lymph vessel beds. EMBO J 2018: e98271. Abstract
Klemm S, Jiang X, Risse B. Deep distance transform to segment visually indistinguishable merged objects. In: Proc. of 40th German Conference on Pattern Recognition (GCPR), Stuttgart 2018: 422-433.
Orlich M, Kiefer F. A qualitative comparison of ten tissue clearing techniques. Histol Histopathol 2018;33: 181-199. Abstract


Hagerling R, Drees D, Scherzinger A, Dierkes C, Martin-Almedina S, Butz S, Gordon K, Schafers M, Hinrichs K, Ostergaard P, Vestweber D, Goerge T, Mansour S, Jiang X, Mortimer PS, Kiefer F. VIPAR, a quantitative approach to 3D histopathology applied to lymphatic malformations. JCI Insight 2017;2: e93424. Abstract


Erapaneedi R, Belousov VV, Schafers M, Kiefer F. A novel family of fluorescent hypoxia sensors reveal strong heterogeneity in tumor hypoxia at the cellular level. Embo J 2016;35: 102-113. Abstract


Lammel U, Bechtold M, Risse B, Berh D, Fleige A, Bunse I, Jiang X, Klambt C, Bogdan S. The Drosophila FHOD1-like formin Knittrig acts through Rok to promote stress fiber formation and directed macrophage migration during the cellular immune response. Development 2014;141: 1366-1380. Abstract


Hägerling R, Pollmann C, Andreas M, Schmidt C, Nurmi H, Adams RH, Alitalo K, Andresen V, Schulte-Merker S, Kiefer F. A novel multistep mechanism for initial lymphangiogenesis in mouse embryos based on ultramicroscopy. EMBO J 2013;32: 629-644. Abstract
Risse B, Thomas S, Otto N, Lopmeier T, Valkov D, Jiang X, Klambt C. FIM, a novel FTIR-based imaging method for high throughput locomotion analysis. PLoS One 2013;8: e53963. Abstract
Sander M, Squarr AJ, Risse B, Jiang X, Bogdan S. Drosophila pupal macrophages--a versatile tool for combined ex vivo and in vivo imaging of actin dynamics at high resolution. Eur J Cell Biol 2013;92: 349-354. Abstract