Immune System variables in healthy subjects and during systemic inflammation

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The clinical research unit addresses the molecular pathophysiological pathways governing systemic inflammation and organ dysfunction in an integrated approach within translational projects. In addition to the individual projects ►P1-10, the aim of the project ►Z is to enforce the translation of results from basic science projects into the clinical setting to develop new diagnostic and therapeutic approaches for the treatment of patients suffering from systemic inflammatory diseases. To this end, all projects have relied on the exchange of scientific expertise, research methods and resources and clinical patient material and samples all brought together in this project. The core project ►Z provides a common connecting interface within the research cluster that will address this urgent need for cooperativity and interactions in between the individual elements of the research network. We provide the research infrastructure to test novel findings from the individual projects regarding their general pathophysiological relevance and clinical translational value. To that end we have also developed and offered sophisticated technologies for in-depth functional ex vivo analysis of patient-derived samples. In particular, by immune phenotyping we provide a very versatile and unmatched tool for the systematical and standardized broad-spectrum analysis of the phenotypic and functional appearance of a very wide array of leukocyte subsets (neutrophils, monocytes, T cells, B cells, NK cells, DCs, etc.) in the context of systemic inflammatory disorders. This approach is complemented by the parallel analysis of soluble markers using multiplex-based analysis system (Luminex 100/200 system) to enable the simultaneous measurement of up to 100 different parameters from a single sample. Furthermore, the project ►Z will also extend its analytical capabilities by inclusion of the Isoplexis IsoSpark technology platform for the dedicated analysis of the immune cell secretome on a single cell basis. By using functional ex vivo assays and imaging flow cytometry we transfer and confirm data obtained in individual projects in clinical cohorts down to specific signaling pathways and transcription factors. All 9 individual projects included in the second funding period of the CRU342 will produce large raw datasets. They are derived from a very wide range of state-of-the-art technology and analyzing such large and complex datasets requires profound bioinformatic knowledge. We bundle the essential statistic expertise in the project ►Z, addressing the inherent challenges of comparison of multiform scientific datasets, improve available and develop novel data analysis strategies and thereby providing biostatistics support to all other projects.