SP 4

Experimental modelling and validation of pneumonia pathophysiology

In this subproject of the CAPSyS consortium, data will be generated in goal-directed in vitro, ex vivo, and in vivo experiments to complement data from clinical cohorts. Important features of pneumonia pathogenesis evade clinical observation as they happen too early before diagnosis, or are inaccessible in the required timely and spatial resolution in patients. For construction and validation of mathematical models in subprojects 1 and 3, manipulation of biological pathways is required, which is impossible in patients. This subproject aims to fill this gap by analyzing central aspects of pneumonia pathology in highly standardized and well-controlled experimental models in vitro, ex vivo, and in vivo. Experimental models will be designed to parallel patient’s course of disease or specific aspects thereof (Figure 1).

Example for the design of the in-vivo pneumonia mouse model, complementing patient data for mathematical modeling.

Further experiments will be hypothesis-driven and focus on promising signaling pathways and specific pathogen and host factors. With increasing progress of mathematical modeling in subprojects 1 and 3, experiments will be designed to address questions and hypotheses resulting from mathematical modeling, leading to an iterative cycle.

Keywords: pneumonia, systems medicine, in vivo experiments, in vitro experiments, ex vivo experiments