Z

Immune System variables in healthy subjects and during systemic inflammation

Principal investigators

KFO 342 Principal investigator Univ.-Prof. Dr. med. Luisa Klotz

Univ.-Prof. Dr. med.

Luisa Klotz

KFO 342 Project coordinator PD Dr. med. Jan Rossaint

Univ.-Prof. Dr. med.

Jan Rossaint

KFO 342 Principal investigator Univ.-Prof. Dr. med. Johannes Roth

Univ.-Prof. Dr. med.

Johannes Roth

Summary

The clinical research unit (CRU) addresses the pathophysiological pathways governing organ dysfunction triggered by systemic inflammation in an integrated approach within translational projects. The project Z will enforce the translation from basic science to the clinical application. All projects rely on the exchange of scientific expertise, research methods, resources and patient material which all will be brought together in this project. The project Z will provide a common interface within the CRU that will address this need for cooperativity and interactions among the projects.

We will provide research infrastructure to test novel findings regarding their general pathophysiological relevance and clinical translational value. We will develop and offer sophisticated technologies for functional ex vivo analysis of patient-derived samples. By immunephenotyping we will provide a very versatile and unmatched tool for the systematic broad-spectrum analysis of the phenotypic and functional appearance of a wide array of leukocyte subsets in the context of systemic inflammatory disorders. This will be complemented by analysis of soluble markers using multiplex-based system to enable the simultaneous measurement of up to 50 different parameters from a single sample. Using functional assays and imaging flow cytometry, we will transfer and confirm data obtained in individual projects in clinical cohorts down to specific signaling pathways.

Picture showing a schematic description.

Integrated Analytic Workflow

Furthermore, the project Z will also investigate the influence of circadian rhythmicity on immune cell recruitment and phenotypic appearance. We know from mouse studies that immune cell behavior follows a distinct circadian rhythmicity. However, these observations are nearly all exclusively derived from the murine system. If and to what extent the immune system variables in humans also follow a circadian pattern remains largely unknown, as does the question if systemic inflammatory disorders would be a variable in this system. This is of great importance for both the basic science research as well as the clinical translational studies since circadian fluctuations may cause a major bias which is generally not considered in clinical studies.

All projects in this CRU will produce large raw datasets derived from a wide range of technologies. Analyzing such complex datasets requires profound bioinformatic knowledge. We will bundle the essential statistic expertise, addressing the challenges of comparison of multiform scientific datasets, improve available and develop novel data analysis strategies. Bringing together the initially project-specific and separated datasets will open up the way towards novel integrated analysis algorithms. Such integrated analyses of basic science and clinical data are only possible within a research network. We hope to transfer basic science results into the clinical context to enable the development of innovative new therapeutic approaches for patients with systemic inflammatory disorders.

Project Team