Priority Research Area Asthma and Allergy
Mission Projects Funding Techniques Publications Staff
The airway epithelium represents the interface between the body and the environment and therefore, encounters inhaled environmental stressors such as allergens, pathogens or noxious agents (e.g. cigarette smoke) first. In chronic airway diseases such as asthma and COPD (chronic obstructive pulmonary disease) the airway epithelium is subject to numerous structural and functional alterations, which impair epithelial integrity and immune homeostasis, thereby playing a significant role in pathogenesis and severity of the diseases. For a better understanding of these disease-associated epithelial alterations, we primarily employ the model system Drosophila melanogaster.
The fruit fly is an ideal in-vivo model for studying airway epithelial dysfunctions typical for respiratory diseases, because
- it lacks an adaptive immune system,
- it has high similarities to the human innate immune system,
- its airways purely comprise epithelial tissue, and
importantly, about 75% of known human disease-related genes have functional orthologs with rather little genetic-redundancy.
(A) Dorsal view of the larval respiratory system of the fruit fly Drosophila melanogaster (modified according to Ruehle 1932).
(B) GFP (green fluorescent protein)-tagged respiratory epithelium of a genetically modified Drosophila larva.
(C-C‘‘) In vivo translocation of a GFP-tagged transcription factor in the respiratory epithelium of Drosophila larva recorded at different time points after cold treatment. (C) Cell nuclei (blue); GFP-tagged transcription factor localised in the cytoplasm (green). (C‘-C‘‘) Cell nuclei (light blue) in which the GFP-tagged transcription factor has been accumulated.
Our research aims to unravel:
- the role of environmental risk factors (e.g. tobacco smoke, nanoparticles) in disease development and worsening,
- the role of the epithelium in airway remodeling, by identifying and exploring signaling pathways and key molecular targets that participate in enhanced airway inflammation and repair,
- the functional relevance of susceptibility genes in airway development and homeostasis (e.g. immunity, integrity) when coping with environmental risk factors during windows of susceptibility (e.g. pregnancy), and
- how prenatal cigarette smoke (CS) exposure promotes the development of chronic airway diseases in subsequent generations. To do this, we focus on evolutionary highly conserved developmental and immunity-related signaling pathways and their key molecular targets that are affected by cigarette-smoke induced epigenetic changes and regulate foetal and infant airway development and growth.
Findings gained from Drosophila will then be extrapolated to mammals by validating them in murine and human bronchial epithelial cell lines (in cooperation with the RG Innate Immunity), primary airway epithelial cells (in cooperation with RG Experimental Pneumology) as well as in murine models of experimental asthma or COPD (in cooperation with the RGs Asthma-Exacerbation & -Regulation and Early Life Origins of Chronic Lung Disease).