Respiratory drug development requires in vitro models that recapitulate disease pathology at the cellular level under well controlled conditions. This is essential for reproducible SAR determination and for iterative lead optimization with chemistry partners such as Zamboni Chemical Solutions.
Well differentiated primary cells that are isolated directly from human lungs enable studies of disease pathogenesis and the impact of environmental factors such as bacterial and viral infection, exposure to cigarette smoke and other pollutants, and inflammatory mediators.
Traffick has access to a biobank of bronchial epithelial cells from >140 lung donors. Non-diseased control cells and cells from individuals with cystic fibrosis, COPD, bronchiectasis and asthma are available as are fibroblasts and alveolar epithelial cells and samples of lung tissue and sputum. Traffick also has access to transgenic mouse models and facilities that may be useful for in vivo validation of drug targets and lead compounds.
In vitro models:
- Submerged human bronchial epithelial (HBE) cells in multiple formats
- Well differentiated epithelial cells cultured at the air liquid interface
- Primary fibroblast cultures
- 3D co-cultures of epithelial cells with fibroblasts
- Vral and non-viral gene delivery and gene knockdown for target validation and analysis
- Transgenic mice
Assays:
- Ussing chamber assays of epithelial transport and barrier function
- Fluorescence and luminescence assays of ROS and cytokine production
- mRNA assays using q-PCR and dd-PCR, protein expression by immunoblotting
- Confocal imaging of live and fixed cells
- Manual and automated (Q-patch) patch clamp electrophysiology
- High throughput screening on multiple platforms
Traffick can utilize these models to:
- Test candidate drugs, hit validation, lead optimization
- Discover and validate novel drug targets
- Examine pathogenesis and molecular mechanisms of drug action
- Perform high throughput screens in relevant cell models
- Provide support for clinical trial activities