Transregional Collaborative Research Center SFB-TR 84 - “Innate Immunity of the Lung: Mechanisms of Pathogen Attack and Host Defence in Pneumonia“

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Z1b-Subproject

Experimental histopathology, advanced histomorphometrical digital image analysis, molecular pathology and tissue banking (Gruber)

 

Observations from single key molecules and their functional integration into relevant pathways are in the focus of most projects within the SFB-TR84 with a tendency towards more and more specialization. Consequently, the Z01b pathology project aims at viewing the significance and implications of experimentally induced single-molecule-based changes in the complex background of the pathology of the entire lungs. Moreover, since many overlapping experimental models are employed within the SFB for different hypotheses and pathways, a networked comparative histopathology and molecular pathology approach will allow to connect different projects to one another for a broader view of cross-talking mechanisms relevant for innate immunity.

Again during the second funding period, almost all partner projects will employ experimental infections of human and/or murine lung tissues with or without genetic manipulations. Based on our profound experiences from the first funding period, we propose to continue the Z01b mouse and human pathology service by a team of experimental pathologists board certified by the European College of Veterinary Pathologists (ECVP). We will continue to provide systematic descriptive histopathology, immunohistochemistry, various aspects of molecular pathology and morphometry. Importantly, we will further introduce and refine high throughput slide scanning and digital morphometrical image analysis tools to improve, speed up and further sensitize the conversion of histomorphological and immunohistochemical information into statistically testable quantitative data. In addition, quality control of established experimental models (e.g., background pathology, comorbidities, lesion interference) as well as the pathological characterization of novel models (phenotyping of new infection models or new genetically engineered mouse lines) will be continued as integrated pathology support for all partners.
A mouse pneumonia and human lung tissue bank has been established during the first funding period with steadily increasing numbers of specimens available to all SFB-TR84 projects. The tissue bank contains cryopreserved or formalin-fixed, paraffin-embedded tissues from all relevant infection models used during the first funding period, enabling both pathology and molecular testing from each tissue. At present (October 2013), tissues from more than 2,000 lungs are included. The bank also includes a variety of other mouse organs from experiments with systemic relevance, e.g., from stroke models. We propose to continue the archiving of all experimental tissues generated during the second funding period for future studies and sharing among other projects. More importantly, all archival tissues from the first funding period will be available for the testing of many of the new hypotheses without the need of performing new animal experiments. Due to the various experimental conditions and pathogens that are increasingly available in this bank, its impact on reducing the numbers of required new experiments will continue to grow during the second funding period.