Neutrophils are ,… smaller amoeboid cells which can easily be stained, with a large polynuclear and fragmented nucleus and faint protoplasma…‘ Elie Metschnikoff. Virchows Arch. 107, 209–249 (1887).
‚…these cells aside from their capacity to stretch out prolongations also are capable of consuming foreign bodies…‘ Elie Metschnikoff. Allg. Wein. med. Ztg. 27/29, 307–332 (1884).
These two statements made by Elie Metschnikoff more than a century ago signify two of the most well-known aspects of neutrophil biology. They are traditionally looked upon as homogenous cell population with an odd-shaped nucleus and they are appreciated for their importance during host defence. Yet, in recent years we have learnt, the neutrophils can adopt different phenotypes and functions and that their functional importance goes beyond infectious diseases and extends to tumour growth and sterile, chronic inflammation.
In the Collaborative Research Centre TRR332 ‘Neutrophils: origin, fate & function’ we aim at delivering an improved understanding of neutrophil biology with specific emphasize on how the local microenvironment shapes neutrophil phenotype and function. Such improved and refined understanding will in the long-run help to not just better understand the actions of neutrophils, but also to interfere with these e.g. in the case of inflammation, infection, and neoplasia. To this end we have assembled 27 principal investigators with a diverse background including clinician scientists, physiologists, biologists, biochemists, pharmacologists, and computer scientists. Importantly, principal investigators with a medical background contribute with a large share thus improving the translational angle of our initiative. Specifically, we have access to various clinical biosamples including atherosclerotic plaques, tumour tissues, tissue from lungs, livers, and kidneys as well as blood and bone marrow samples. In addition, modelling disease states in animals will help to understand the pathological roles of neutrophils in disease and permit generation and testing of interference strategies.
Technical advances are key to innovative research. This CRC features several recent technical advancements in the central project Z1 that allow to visualise neutrophils in context. These include: Multiplex antibody-based imaging (MABI) using the MACSima™ Imaging Platform - a cyclic immunofluorescence imaging platform enabling fully automated immunofluorescence imaging of individual biological specimens. The system operates by iterative fluorescent staining, image acquisition, and signal erasure, using multiple fluorochrome-labelled antibodies per cycle. Matrix-assisted laser desorption ionization (MALDI) imaging allows an acquisition of in situ MALDI spectra allowing discovery-driven and comprehensive molecular understanding of the tissue microenvironment by determining the distribution of lipids, further secondary metabolites, glycans, proteins (following tryptic on-tissue digestion) and pharmaceuticals. Co-registration of MABI and MALDI data sets - to determine the function of neutrophils within the different tissue segments, and to decode the tissue microenvironment that dictates the phenotype, fate and function of neutrophils, co-registration of MABI and MALDI data sets acquired from the same tissue section will be utilized. The combination of these two imaging techniques will permit to overlay high resolution antibody-based imaging data of mostly low-abundant cell surface markers with spatial information on metabolites, lipids, and peptides.
This CRC TRR332 brings together experts from three applicant universities, the WWU Münster, the LMU Munich, and the University Duisburg-Essen as well as two associated institutions, namely the TU Dresden and the ISAS Leibniz Institute Dortmund. With its distribution across five partner sites a central structure for data exchange is essential. Hence, within the INF project led by the WWU IT department a structure for central storage and data management as well as for sharing of licensed software will be established and hosted within the WWU cloud. It is an important mission of this CRC to advance equal opportunities and to support early career scientists. Please explore specifics on the measures we take on our webpage.
Our CRC clearly benefited from various CRCs at the partner sites that had been established several years ago including the CRC914 in Munich and the CRC1009 in Münster. With these serving as breeding grounds for our ideas, we have met first time in January 2019 to discuss a neutrophil-centred consortium. After more than three years of work, our network receives substantial funding from the German Research Foundation from July 2022 on for initially four years. We hope that our research centre will make a major contribution to the rapidly evolving neutrophil community.